Skip to main content

Advertisement

SpringerLink
Log in

Roles of SIRT6 in kidney disease: a novel therapeutic target

  • Review
  • Published:
Cellular and Molecular Life Sciences Aims and scope Submit manuscript

Abstract

SIRT6 is an NAD+ dependent deacetylase that belongs to the mammalian sirtuin family. SIRT6 is mainly located in the nucleus and regulates chromatin remodeling, genome stability, and gene transcription. SIRT6 extensively participates in various physiological activities such as DNA repair, energy metabolism, oxidative stress, inflammation, and fibrosis. In recent years, the role of epigenetics such as acetylation modification in renal disease has gradually received widespread attention. SIRT6 reduces oxidative stress, inflammation, and renal fibrosis, which is of great importance in maintaining cellular homeostasis and delaying the chronic progression of kidney disease. Here, we review the structure and biological function of SIRT6 and summarize the regulatory mechanisms of SIRT6 in kidney disease. Moreover, the role of SIRT6 as a potential therapeutic target for the progression of kidney disease will be discussed.

Graphical abstract

SIRT6 plays an important role in kidney disease. SIRT6 regulates mitochondrial dynamics and mitochondrial biogenesis, induces G2/M cycle arrest, and plays an antioxidant role in nephrotoxicity, IR, obstructive nephropathy, and sepsis-induced AKI. SIRT6 prevents and delays progressive CKD induced by hyperglycemia, kidney senescence, hypertension, and lipid accumulation by regulating mitochondrial biogenesis, and has antioxidant, anti-inflammatory, and antifibrosis effects. Additionally, hypoxia, inflammation, and fibrosis are the main mechanisms of the AKI-to-CKD transition. SIRT6 plays a critical role in the AKI-to-CKD transition and kidney repair through anti-inflammatory, antifibrotic, and mitochondrial quality control mechanisms. AKI Acute kidney injury, CKD Chronic kidney disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Availability of data and materials

Not applicable.

References

  1. Bhargava P, Schnellmann RG (2017) Mitochondrial energetics in the kidney. Nat Rev Nephrol 13(10):629–646. https://doi.org/10.1038/nrneph.2017.107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Ferenbach DA, Bonventre JV (2015) Mechanisms of maladaptive repair after AKI leading to accelerated kidney ageing and CKD. Nat Rev Nephrol 11(5):264–276. https://doi.org/10.1038/nrneph.2015.3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Kim MG, Yang J, Ko YS, Lee HY, Oh SW, Cho WY, Jo SK (2019) Impact of aging on transition of acute kidney injury to chronic kidney disease. Sci Rep 9(1):18445. https://doi.org/10.1038/s41598-019-54585-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Morigi M, Perico L, Benigni A (2018) Sirtuins in renal health and disease. J Am Soc Nephrol 29(7):1799–1809. https://doi.org/10.1681/ASN.2017111218

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Hershberger KA, Martin AS, Hirschey MD (2017) Role of NAD and mitochondrial sirtuins in cardiac and renal diseases. Nat Rev Nephrol 13(4):213–225. https://doi.org/10.1038/nrneph.2017.5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Frye RA (2000) Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins. Biochem Biophys Res Commun 273(2):793–798. https://doi.org/10.1006/bbrc.2000.3000

    Article  CAS  PubMed  Google Scholar 

  7. Tanno M, Sakamoto J, Miura T, Shimamoto K, Horio Y (2007) Nucleocytoplasmic shuttling of the NAD+-dependent histone deacetylase SIRT1. J Biol Chem 282(9):6823–6832. https://doi.org/10.1074/jbc.M609554200

    Article  CAS  PubMed  Google Scholar 

  8. Hamaidi I, Zhang L, Kim N, Wang MH, Iclozan C, Fang B, Liu M, Koomen JM, Berglund AE, Yoder SJ, Yao J, Engelman RW, Creelan BC, Conejo-Garcia JR, Antonia SJ, Mulé JJ, Kim S (2020) Sirt2 inhibition enhances metabolic fitness and effector functions of tumor-reactive T cells. Cell Metab 32(3):420–436. https://doi.org/10.1016/j.cmet.2020.07.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Samant SA, Zhang HJ, Hong Z, Pillai VB, Sundaresan NR, Wolfgeher D, Archer SL, Chan DC, Gupta MP (2014) SIRT3 deacetylates and activates OPA1 to regulate mitochondrial dynamics during stress. Mol Cell Biol 34(5):807–819. https://doi.org/10.1128/MCB.01483-13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Wang YS, Du L, Liang X, Meng P, Bi L, Wang YL, Wang C, Tang B (2019) Sirtuin 4 depletion promotes hepatocellular carcinoma tumorigenesis through regulating adenosine-monophosphate-activated protein kinase alpha/mammalian target of rapamycin axis in mice. Hepatology 69(4):1614–1631. https://doi.org/10.1002/hep.30421

    Article  CAS  PubMed  Google Scholar 

  11. Zhang Y, Bharathi SS, Rardin MJ, Lu J, Maringer KV, Sims-Lucas S, Prochownik EV, Gibson BW, Goetzman ES (2017) Lysine desuccinylase SIRT5 binds to cardiolipin and regulates the electron transport chain. J Biol Chem 292(24):10239–10249. https://doi.org/10.1074/jbc.M117.785022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Gertler AA, Cohen HY (2013) SIRT6, a protein with many faces. Biogerontology 14(6):629–639. https://doi.org/10.1007/s10522-013-9478-8

    Article  CAS  PubMed  Google Scholar 

  13. Yu AQ, Wang J, Jiang ST, Yuan LQ, Ma HY, Hu YM, Han XM, Tan LM, Wang ZX (2021) SIRT7-induced PHF5A decrotonylation regulates aging progress through alternative splicing-mediated downregulation of CDK2. Front Cell Dev Biol 9:710479. https://doi.org/10.3389/fcell.2021.710479

    Article  PubMed  PubMed Central  Google Scholar 

  14. Ford E, Voit R, Liszt G, Magin C, Grummt I, Guarente L (2006) Mammalian Sir2 homolog SIRT7 is an activator of RNA polymerase I transcription. Genes Dev 20(9):1075–1080. https://doi.org/10.1101/gad.1399706

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Gewin LS (2020) Sirtuin 6 and renal injury: another link in the β-catenin chain? Kidney Int 97(1):24–27. https://doi.org/10.1016/j.kint.2019.09.022

    Article  CAS  PubMed  Google Scholar 

  16. Cai J, Liu Z, Huang X, Shu S, Hu X, Zheng M, Tang C, Liu Y, Chen G, Sun L, Liu H, Liu F, Cheng J, Dong Z (2020) The deacetylase sirtuin 6 protects against kidney fibrosis by epigenetically blocking β-catenin target gene expression. Kidney Int 97(1):106–118. https://doi.org/10.1016/j.kint.2019.08.028

    Article  CAS  PubMed  Google Scholar 

  17. Wei W, Guo X, Gu L, Jia J, Yang M, Yuan W, Rong S (2021) Bone marrow mesenchymal stem cell exosomes suppress phosphate-induced aortic calcification via SIRT6-HMGB1 deacetylation. Stem Cell Res Ther 12(1):235. https://doi.org/10.1186/s13287-021-02307-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Tennen RI, Berber E, Chua KF (2010) Functional dissection of SIRT6: identification of domains that regulate histone deacetylase activity and chromatin localization. Mech Ageing Dev 131(3):185–192. https://doi.org/10.1016/j.mad.2010.01.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Pan PW, Feldman JL, Devries MK, Dong A, Edwards AM, Denu JM (2011) Structure and biochemical functions of SIRT6. J Biol Chem 286(16):14575–14587. https://doi.org/10.1074/jbc.M111.218990

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Chang AR, Ferrer CM, Mostoslavsky R (2020) SIRT6, a mammalian deacylase with multitasking abilities. Physiol Rev 100(1):145–169. https://doi.org/10.1152/physrev.00030.2018

    Article  CAS  PubMed  Google Scholar 

  21. Jiang H, Khan S, Wang Y, Charron G, He B, Sebastian C, Du J, Kim R, Ge E, Mostoslavsky R, Hang HC, Hao Q, Lin H (2013) SIRT6 regulates TNF-alpha secretion through hydrolysis of long-chain fatty acyl lysine. Nature 496(7443):110–113. https://doi.org/10.1038/nature12038

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Michishita E, McCord RA, Berber E, Kioi M, Padilla-Nash H, Damian M, Cheung P, Kusumoto R, Kawahara TL, Barrett JC, Chang HY, Bohr VA, Ried T, Gozani O, Chua KF (2008) SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin. Nature 452(7186):492–496. https://doi.org/10.1038/nature06736

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Michishita E, McCord RA, Boxer LD, Barber MF, Hong T, Gozani O, Chua KF (2009) Cell cycle-dependent deacetylation of telomeric histone H3 lysine K56 by human SIRT6. Cell Cycle 8(16):2664–2666. https://doi.org/10.4161/cc.8.16.9367

    Article  CAS  PubMed  Google Scholar 

  24. Tasselli L, Xi Y, Zheng W, Tennen RI, Odrowaz Z, Simeoni F, Li W, Chua KF (2016) SIRT6 deacetylates H3K18ac at pericentric chromatin to prevent mitotic errors and cellular senescence. Nat Struct Mol Biol 23(5):434–440. https://doi.org/10.1038/nsmb.3202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Liu G, Chen H, Liu H, Zhang W, Zhou J (2021) Emerging roles of SIRT6 in human diseases and its modulators. Med Res Rev 41(2):1089–1137. https://doi.org/10.1002/med.21753

    Article  PubMed  Google Scholar 

  26. Kugel S, Mostoslavsky R (2014) Chromatin and beyond: the multitasking roles for SIRT6. Trends Biochem Sci 39(2):72–81. https://doi.org/10.1016/j.tibs.2013.12.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Tennen RI, Bua DJ, Wright WE, Chua KF (2011) SIRT6 is required for maintenance of telomere position effect in human cells. Nat Commun 2:433. https://doi.org/10.1038/ncomms1443

    Article  CAS  PubMed  Google Scholar 

  28. Hou T, Cao Z, Zhang J, Tang M, Tian Y, Li Y, Lu X, Chen Y, Wang H, Wei FZ, Wang L, Yang Y, Zhao Y, Wang Z, Wang H, Zhu WG (2020) SIRT6 coordinates with CHD4 to promote chromatin relaxation and DNA repair. Nucleic Acids Res 48(6):2982–3000. https://doi.org/10.1093/nar/gkaa006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Aleksandrov R, Hristova R, Stoynov S, Gospodinov A (2020) The chromatin response to double-strand DNA breaks and their repair. Cells 9(8):1853. https://doi.org/10.3390/cells9081853

    Article  CAS  PubMed Central  Google Scholar 

  30. Onn L, Portillo M, Ilic S, Cleitman G, Stein D, Kaluski S, Shirat I, Slobodnik Z, Einav M, Erdel F, Akabayov B, Toiber D (2020) SIRT6 is a DNA double-strand break sensor. Elife 9:e51636. https://doi.org/10.7554/eLife.51636

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Koczor CA, Saville KM, Andrews JF, Clark J, Fang Q, Li J, Al-Rahahleh RQ, Ibrahim M, McClellan S, Makarov MV, Migaud ME, Sobol RW (2021) Temporal dynamics of base excision/single-strand break repair protein complex assembly/disassembly are modulated by the PARP/NAD+/SIRT6 axis. Cell Rep 37(5):109917. https://doi.org/10.1016/j.celrep.2021.109917

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Mostoslavsky R, Chua KF, Lombard DB, Pang WW, Fischer MR, Gellon L, Liu P, Mostoslavsky G, Franco S, Murphy MM, Mills KD, Patel P, Hsu JT, Hong AL, Ford E, Cheng HL, Kennedy C, Nunez N, Bronson R, Frendewey D, Auerbach W, Valenzuela D, Karow M, Hottiger MO, Hursting S, Barrett JC, Guarente L, Mulligan R, Demple B, Yancopoulos GD, Alt FW (2006) Genomic instability and aging-like phenotype in the absence of mammalian SIRT6. Cell 124(2):315–329. https://doi.org/10.1016/j.cell.2005.11.044

    Article  CAS  PubMed  Google Scholar 

  33. Toiber D, Erdel F, Bouazoune K, Silberman DM, Zhong L, Mulligan P, Sebastian C, Cosentino C, Martinez-Pastor B, Giacosa S, D’Urso A, Näär AM, Kingston R, Rippe K, Mostoslavsky R (2013) SIRT6 recruits SNF2H to DNA break sites, preventing genomic instability through chromatin remodeling. Mol Cell 51(4):454–468. https://doi.org/10.1016/j.molcel.2013.06.018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Meng F, Qian M, Peng B, Peng L, Wang X, Zheng K, Liu Z, Tang X, Zhang S, Sun S, Cao X, Pang Q, Zhao B, Ma W, Songyang Z, Xu B, Zhu WG, Xu X, Liu B (2020) Synergy between SIRT1 and SIRT6 helps recognize DNA breaks and potentiates the DNA damage response and repair in humans and mice. Elife 9:e55828. https://doi.org/10.7554/eLife.55828

    Article  PubMed  PubMed Central  Google Scholar 

  35. Bakewell S, Conde I, Fallah Y, McCoy M, Jin L, Shajahan-Haq AN (2020) Inhibition of DNA repair pathways and induction of ROS are potential mechanisms of action of the small molecule inhibitor BOLD-100 in breast cancer. Cancers (Basel) 12(9):2647. https://doi.org/10.3390/cancers12092647

    Article  CAS  Google Scholar 

  36. Mao Z, Hine C, Tian X, Van Meter M, Au M, Vaidya A, Seluanov A, Gorbunova V (2011) SIRT6 promotes DNA repair under stress by activating PARP1. Science 332(6036):1443–1446. https://doi.org/10.1126/science.1202723

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Van Meter M, Simon M, Tombline G, May A, Morello TD, Hubbard BP, Bredbenner K, Park R, Sinclair DA, Bohr VA, Gorbunova V, Seluanov A (2016) JNK phosphorylates SIRT6 to stimulate DNA double-strand break repair in response to oxidative stress by recruiting PARP1 to DNA breaks. Cell Rep 16(10):2641–2650. https://doi.org/10.1016/j.celrep.2016.08.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Mao Z, Tian X, Van Meter M, Ke Z, Gorbunova V, Seluanov A (2012) Sirtuin 6 (SIRT6) rescues the decline of homologous recombination repair during replicative senescence. Proc Natl Acad Sci USA 109(29):11800–11805. https://doi.org/10.1073/pnas.1200583109

    Article  PubMed  PubMed Central  Google Scholar 

  39. Rizzo A, Iachettini S, Salvati E, Zizza P, Maresca C, D’Angelo C, Benarroch-Popivker D, Capolupo A, Del Gaudio F, Cosconati S, Di Maro S, Merlino F, Novellino E, Amoreo CA, Mottolese M, Sperduti I, Gilson E, Biroccio A (2017) SIRT6 interacts with TRF2 and promotes its degradation in response to DNA damage. Nucleic Acids Res 45(4):1820–1834. https://doi.org/10.1093/nar/gkw1202

    Article  CAS  PubMed  Google Scholar 

  40. Tan J, Wang X, Hwang BJ, Gonzales R, Konen O, Lan L, Lu AL (2020) An ordered assembly of MYH glycosylase, SIRT6 protein deacetylase, and Rad9-Rad1-Hus1 checkpoint clamp at oxidatively damaged telomeres. Aging (Albany NY) 12(18):17761–17785. https://doi.org/10.18632/aging.103934

    Article  CAS  Google Scholar 

  41. Geng A, Tang H, Huang J, Qian Z, Qin N, Yao Y, Xu Z, Chen H, Lan L, Xie H, Zhang J, Jiang Y, Mao Z (2020) The deacetylase SIRT6 promotes the repair of UV-induced DNA damage by targeting DDB2. Nucleic Acids Res 48(16):9181–9194. https://doi.org/10.1093/nar/gkaa661

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Rezazadeh S, Yang D, Biashad SA, Firsanov D, Takasugi M, Gilbert M, Tombline G, Bhanu NV, Garcia BA, Seluanov A, Gorbunova V (2020) SIRT6 mono-ADP ribosylates KDM2A to locally increase H3K36me2 at DNA damage sites to inhibit transcription and promote repair. Aging (Albany NY) 12(12):11165–11184. https://doi.org/10.18632/aging.103567

    Article  CAS  Google Scholar 

  43. Fan Y, Cheng J, Yang Q, Feng J, Hu J, Ren Z, Yang H, Yang D, Ding G (2021) Sirt6-mediated Nrf2/HO-1 activation alleviates angiotensin II-induced DNA DSBs and apoptosis in podocytes. Food Funct 12(17):7867–7882. https://doi.org/10.1039/d0fo03467c

    Article  CAS  PubMed  Google Scholar 

  44. Wang S, Zhang J, Deng X, Zhao Y, Xu K (2020) Advances in characterization of SIRT3 deacetylation targets in mitochondrial function. Biochimie 179:1–13. https://doi.org/10.1016/j.biochi.2020.08.021

    Article  CAS  PubMed  Google Scholar 

  45. Wang Y, Zhang X, Wang P, Shen Y, Yuan K, Li M, Liang W, Que H (2019) Sirt3 overexpression alleviates hyperglycemia-induced vascular inflammation through regulating redox balance, cell survival, and AMPK-mediated mitochondrial homeostasis. J Recept Signal Transduct Res 39(4):341–349. https://doi.org/10.1080/10799893.2019.1684521

    Article  CAS  PubMed  Google Scholar 

  46. Wang Q, Xu J, Li X, Liu Z, Han Y, Xu X, Li X, Tang Y, Liu Y, Yu T, Li X (2019) Sirt3 modulate renal ischemia-reperfusion injury through enhancing mitochondrial fusion and activating the ERK-OPA1 signaling pathway. J Cell Physiol 234(12):23495–23506. https://doi.org/10.1002/jcp.28918

    Article  CAS  PubMed  Google Scholar 

  47. Kanwal A, Pillai VB, Samant S, Gupta M, Gupta MP (2019) The nuclear and mitochondrial sirtuins, Sirt6 and Sirt3, regulate each other’s activity and protect the heart from developing obesity-mediated diabetic cardiomyopathy. FASEB J 33(10):10872–10888. https://doi.org/10.1096/fj.201900767R

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Pan H, Guan D, Liu X, Li J, Wang L, Wu J, Zhou J, Zhang W, Ren R, Zhang W, Li Y, Yang J, Hao Y, Yuan T, Yuan G, Wang H, Ju Z, Mao Z, Li J, Qu J, Tang F, Liu GH et al (2016) SIRT6 safeguards human mesenchymal stem cells from oxidative stress by coactivating NRF2. Cell res 26(2):190–205. https://doi.org/10.1038/cr.2016.4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Zhang W, Wei R, Zhang L, Tan Y, Qian C (2017) Sirtuin 6 protects the brain from cerebral ischemia/reperfusion injury through NRF2 activation. Neuroscience 366:95–104. https://doi.org/10.1016/j.neuroscience.2017.09.035

    Article  CAS  PubMed  Google Scholar 

  50. Kasai S, Shimizu S, Tatara Y, Mimura J, Itoh K (2020) Regulation of Nrf2 by mitochondrial reactive oxygen species in physiology and pathology. Biomolecules 10(2):320. https://doi.org/10.3390/biom10020320

    Article  CAS  PubMed Central  Google Scholar 

  51. Fan Y, Yang Q, Yang Y, Gao Z, Ma Y, Zhang L, Liang W, Ding G (2019) Sirt6 suppresses high glucose-induced mitochondrial dysfunction and apoptosis in podocytes through AMPK activation. Int J Biol Sci 15(3):701–713. https://doi.org/10.7150/ijbs.29323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Li Z, Xu K, Guo Y, Ping L, Gao Y, Qiu Y, Ni J, Liu Q, Wang Z (2020) A high-fat diet reverses metabolic disorders and premature aging by modulating insulin and IGF1 signaling in SIRT6 knockout mice. Aging Cell 19(3):e13104. https://doi.org/10.1111/acel.13104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Kuang J, Chen L, Tang Q, Zhang J, Li Y, He J (2018) The role of Sirt6 in obesity and diabetes. Front Physiol 9:135. https://doi.org/10.3389/fphys.2018.00135

    Article  PubMed  PubMed Central  Google Scholar 

  54. Song MY, Kim SH, Ryoo GH, Kim MK, Cha HN, Park SY, Hwang HP, Yu HC, Bae EJ, Park BH (2019) Adipose sirtuin 6 drives macrophage polarization toward M2 through IL-4 production and maintains systemic insulin sensitivity in mice and humans. Exp Mol Med 51(5):1–10. https://doi.org/10.1038/s12276-019-0256-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Zhong L, D’Urso A, Toiber D, Sebastian C, Henry RE, Vadysirisack DD, Guimaraes A, Marinelli B, Wikstrom JD, Nir T, Clish CB, Vaitheesvaran B, Iliopoulos O, Kurland I, Dor Y, Weissleder R, Shirihai OS, Ellisen LW, Espinosa JM, Mostoslavsky R (2010) The histone deacetylase Sirt6 regulates glucose homeostasis via Hif1alpha. Cell 140(2):280–293. https://doi.org/10.1016/j.cell.2009.12.041

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Roichman A, Elhanati S, Aon MA, Abramovich I, Di Francesco A, Shahar Y, Avivi MY, Shurgi M, Rubinstein A, Wiesner Y, Shuchami A, Petrover Z, Lebenthal-Loinger I, Yaron O, Lyashkov A, Ubaida-Mohien C, Kanfi Y, Lerrer B, Fernández-Marcos PJ, Serrano M, Gottlieb E, de Cabo R, Cohen HY et al (2021) Restoration of energy homeostasis by SIRT6 extends healthy lifespan. Nat Commun 12(1):3208. https://doi.org/10.1038/s41467-021-23545-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Xiao C, Kim HS, Lahusen T, Wang RH, Xu X, Gavrilova O, Jou W, Gius D, Deng CX (2010) SIRT6 deficiency results in severe hypoglycemia by enhancing both basal and insulin-stimulated glucose uptake in mice. J Biol Chem 285(47):36776–36784. https://doi.org/10.1074/jbc.M110.168039

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Gu L, Ding X, Wang Y, Gu M, Zhang J, Yan S, Li N, Song Z, Yin J, Lu L, Peng Y (2019) Spexin alleviates insulin resistance and inhibits hepatic gluconeogenesis via the FoxO1/PGC-1α pathway in high-fat-diet-induced rats and insulin resistant cells. Int J Biol Sci 15(13):2815–2829. https://doi.org/10.7150/ijbs.31781

    Article  PubMed  PubMed Central  Google Scholar 

  59. Shi MY, Bang IH, Han CY, Lee DH, Park BH, Bae EJ (2020) Statin suppresses sirtuin 6 through miR-495, increasing FoxO1-dependent hepatic gluconeogenesis. Theranostics 10(25):11416–11427. https://doi.org/10.7150/thno.49770

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Dominy JE Jr, Lee Y, Jedrychowski MP, Chim H, Jurczak MJ, Camporez JP, Ruan HB, Feldman J, Pierce K, Mostoslavsky R, Denu JM, Clish CB, Yang X, Shulman GI, Gygi SP, Puigserver P (2012) The deacetylase Sirt6 activates the acetyltransferase GCN5 and suppresses hepatic gluconeogenesis. Mol Cell 48(6):900–913. https://doi.org/10.1016/j.molcel.2012.09.030

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Kuang J, Zhang Y, Liu Q, Shen J, Pu S, Cheng S, Chen L, Li H, Wu T, Li R, Li Y, Zou M, Zhang Z, Jiang W, Xu G, Qu A, Xie W, He J (2017) Fat-specific Sirt6 ablation sensitizes mice to high-fat diet-induced obesity and insulin resistance by inhibiting lipolysis. Diabetes 66(5):1159–1171. https://doi.org/10.2337/db16-1225

    Article  CAS  PubMed  Google Scholar 

  62. Kim HS, Xiao C, Wang RH, Lahusen T, Xu X, Vassilopoulos A, Vazquez-Ortiz G, Jeong WI, Park O, Ki SH, Gao B, Deng CX (2010) Hepatic-specific disruption of SIRT6 in mice results in fatty liver formation due to enhanced glycolysis and triglyceride synthesis. Cell Metab 12(3):224–236. https://doi.org/10.1016/j.cmet.2010.06.009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Kanfi Y, Peshti V, Gil R, Naiman S, Nahum L, Levin E, Kronfeld-Schor N, Cohen HY (2010) SIRT6 protects against pathological damage caused by diet-induced obesity. Aging Cell 9(2):162–173. https://doi.org/10.1111/j.1474-9726.2009.00544.x

    Article  CAS  PubMed  Google Scholar 

  64. Khan D, Ara T, Ravi V, Rajagopal R, Tandon H, Parvathy J, Gonzalez EA, Asirvatham-Jeyaraj N, Krishna S, Mishra S, Raghu S, Bhati AS, Tamta AK, Dasgupta S, Kolthur-Seetharam U, Etchegaray JP, Mostoslavsky R, Rao PSM, Srinivasan N, Sundaresan NR (2021) SIRT6 transcriptionally regulates fatty acid transport by suppressing PPARγ. Cell Rep 35(9):109190. https://doi.org/10.1016/j.celrep.2021.109190

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Ren S, Hou Y, Zuo Z, Liu Z, Wang H, Xu Y, Yamamoto M, Zhang Q, Fu J, Pi J (2020) Protracted rosiglitazone treatment exacerbates inflammation in white adipose tissues of adipocyte-specific Nfe2l1 knockout mice. Food Chem Toxicol 146:111836. https://doi.org/10.1016/j.fct.2020.111836

    Article  CAS  PubMed  Google Scholar 

  66. Yang SJ, Choi JM, Chae SW, Kim WJ, Park SE, Rhee EJ, Lee WY, Oh KW, Park SW, Kim SW, Park CY (2011) Activation of peroxisome proliferator-activated receptor gamma by rosiglitazone increases sirt6 expression and ameliorates hepatic steatosis in rats. PLoS ONE 6(2):e17057. https://doi.org/10.1371/journal.pone.0017057

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Elhanati S, Kanfi Y, Varvak A, Roichman A, Carmel-Gross I, Barth S, Gibor G, Cohen HY (2013) Multiple regulatory layers of SREBP1/2 by SIRT6. Cell Rep 4(5):905–912. https://doi.org/10.1016/j.celrep.2013.08.006

    Article  CAS  PubMed  Google Scholar 

  68. Tao R, Xiong X, DePinho RA, Deng CX, Dong XC (2013) FoxO3 transcription factor and Sirt6 deacetylase regulate low density lipoprotein (LDL)-cholesterol homeostasis via control of the proprotein convertase subtilisin/kexin type 9 (Pcsk9) gene expression. J Biol Chem 288(41):29252–29259. https://doi.org/10.1074/jbc.M113.481473

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Luo P, Qin C, Zhu L, Fang C, Zhang Y, Zhang H, Pei F, Tian S, Zhu XY, Gong J, Mao Q, Xiao C, Su Y, Zheng H, Xu T, Lu J, Zhang J (2018) Ubiquitin-specific peptidase 10 (USP10) inhibits hepatic steatosis, insulin resistance, and inflammation through Sirt6. Hepatology 68(5):1786–1803. https://doi.org/10.1002/hep.30062

    Article  CAS  PubMed  Google Scholar 

  70. Yang Q, Hu J, Yang Y, Chen Z, Feng J, Zhu Z, Wang H, Yang D, Liang W, Ding G (2020) Sirt6 deficiency aggravates angiotensin II-induced cholesterol accumulation and injury in podocytes. Theranostics 10(16):7465–7479. https://doi.org/10.7150/thno.45003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Zhuang J, Pan ZJ, Mengqiu-Li HFS, Zhu CK, Wu N, Chang G, Wang H, Zhao XX (2020) BDE-47 induced apoptosis in zebrafish embryos through mitochondrial ROS-mediated JNK signaling. Chemosphere 258:127385. https://doi.org/10.1016/j.chemosphere.2020.127385

    Article  CAS  PubMed  Google Scholar 

  72. Lin Q, Li S, Jiang N, Shao X, Zhang M, Jin H, Zhang Z, Shen J, Zhou Y, Zhou W, Gu L, Lu R, Ni Z (2019) PINK1-parkin pathway of mitophagy protects against contrast-induced acute kidney injury via decreasing mitochondrial ROS and NLRP3 inflammasome activation. Redox Biol 26:101254. https://doi.org/10.1016/j.redox.2019.101254

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Chen CC, Chang ZY, Tsai FJ, Chen SY (2020) Resveratrol pretreatment ameliorates concanavalin A-induced advanced renal glomerulosclerosis in aged mice through upregulation of sirtuin 1-mediated Klotho expression. Int J Mol Sci 21(18):6766. https://doi.org/10.3390/ijms21186766

    Article  CAS  PubMed Central  Google Scholar 

  74. Salama RM, Nasr MM, Abdelhakeem JI, Roshdy OK, ElGamal MA (2020) Alogliptin attenuates cyclophosphamide-induced nephrotoxicity: a novel therapeutic approach through modulating MAP3K/JNK/SMAD3 signaling cascade. Drug Chem Toxicol. https://doi.org/10.1080/01480545.2020.1814319

    Article  PubMed  Google Scholar 

  75. Suzuki T, Yamamoto M (2015) Molecular basis of the Keap1-Nrf2 system. Free Radic Biol Med 88(Pt B):93–100. https://doi.org/10.1016/j.freeradbiomed.2015.06.006

    Article  CAS  PubMed  Google Scholar 

  76. Yang Y, Tian T, Wang Y, Li Z, Xing K, Tian G (2019) SIRT6 protects vascular endothelial cells from angiotensin II-induced apoptosis and oxidative stress by promoting the activation of Nrf2/ARE signaling. Eur J Pharmacol 859:172516. https://doi.org/10.1016/j.ejphar.2019.172516

    Article  CAS  PubMed  Google Scholar 

  77. Fan X, Wei W, Huang J, Liu X, Ci X (2020) Isoorientin attenuates cisplatin-induced nephrotoxicity through the inhibition of oxidative stress and apoptosis via activating the SIRT1/SIRT6/Nrf-2 pathway. Front Pharmacol 11:264. https://doi.org/10.3389/fphar.2020.00264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. D’Onofrio N, Sardu C, Trotta MC, Scisciola L, Turriziani F, Ferraraccio F, Panarese I, Petrella L, Fanelli M, Modugno P, Massetti M, Marfella LV, Sasso FC, Rizzo MR, Barbieri M, Furbatto F, Minicucci F, Mauro C, Federici M, Balestrieri ML, Paolisso G, Marfella R (2021) Sodium-glucose co-transporter 2 expression and inflammatory activity in diabetic atherosclerotic plaques: Effects of sodium-glucose co-transporter 2 inhibitor treatment. Mol Metab 54:101337. https://doi.org/10.1016/j.molmet.2021.101337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Takahashi M, Higuchi M, Makokha GN, Matsuki H, Yoshita M, Tanaka Y, Fujii M (2013) HTLV-1 tax oncoprotein stimulates ROS production and apoptosis in T cells by interacting with USP10. Blood 122(5):715–725. https://doi.org/10.1182/blood-2013-03-493718

    Article  CAS  PubMed  Google Scholar 

  80. Gao F, Qian M, Liu G, Ao W, Dai D, Yin C (2021) USP10 alleviates sepsis-induced acute kidney injury by regulating Sirt6-mediated Nrf2/ARE signaling pathway. J Inflamm (Lond) 18(1):25. https://doi.org/10.1186/s12950-021-00291-7

    Article  CAS  Google Scholar 

  81. Li J, Yu D, Chen S, Liu Y, Shi J, Zhang J, Wen P, Wang Z, Li J, Guo W, Zhang S (2020) Sirt6 opposes glycochenodeoxycholate-induced apoptosis of biliary epithelial cells through the AMPK/PGC-1alpha pathway. Cell Biosci 10:43. https://doi.org/10.1186/s13578-020-00402-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. He Y, Xiao Y, Yang X, Li Y, Wang B, Yao F, Shang C, Jin Z, Wang W, Lin R (2017) SIRT6 inhibits TNF-alpha-induced inflammation of vascular adventitial fibroblasts through ROS and Akt signaling pathway. Exp Cell Res 357(1):88–97. https://doi.org/10.1016/j.yexcr.2017.05.001

    Article  CAS  PubMed  Google Scholar 

  83. Shao J, Yang X, Liu T, Zhang T, Xie QR, Xia W (2016) Autophagy induction by SIRT6 is involved in oxidative stress-induced neuronal damage. Protein Cell 7(4):281–290. https://doi.org/10.1007/s13238-016-0257-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Li W, Liu X, Qiao H (2020) Downregulation of hippocampal SIRT6 activates AKT/CRMP2 signaling and ameliorates chronic stress-induced depression-like behavior in mice. Acta Pharmacol Sin 41(12):1557–1567. https://doi.org/10.1038/s41401-020-0387-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Wang XX, Wang XL, Tong MM, Gan L, Chen H, Wu SS, Chen JX, Li RL, Wu Y, Zhang HY, Zhu Y, Li YX, He JH, Wang M, Jiang W (2016) SIRT6 protects cardiomyocytes against ischemia/reperfusion injury by augmenting FoxO3α-dependent antioxidant defense mechanisms. Basic Res Cardiol 111(2):13. https://doi.org/10.1007/s00395-016-0531-z

    Article  CAS  PubMed  Google Scholar 

  86. Vitiello M, Zullo A, Servillo L, Mancini FP, Borriello A, Giovane A, Della Ragione F, D’Onofrio N, Balestrieri ML (2017) Multiple pathways of SIRT6 at the crossroads in the control of longevity, cancer, and cardiovascular diseases. Ageing Res Rev 35:301–311. https://doi.org/10.1016/j.arr.2016.10.008

    Article  CAS  PubMed  Google Scholar 

  87. Santos-Barriopedro I, Bosch-Presegué L, Marazuela-Duque A, de la Torre C, Colomer C, Vazquez BN, Fuhrmann T, Martínez-Pastor B, Lu W, Braun T, Bober E, Jenuwein T, Serrano L, Esteller M, Chen Z, Barceló-Batllori S, Mostoslavsky R, Espinosa L, Vaquero A (2018) SIRT6-dependent cysteine monoubiquitination in the PRE-SET domain of Suv39h1 regulates the NF-κB pathway. Nat Commun 9(1):101. https://doi.org/10.1038/s41467-017-02586-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Tang SCW, Yiu WH (2020) Innate immunity in diabetic kidney disease. Nat Rev Nephrol 16(4):206–222. https://doi.org/10.1038/s41581-019-0234-4

    Article  CAS  PubMed  Google Scholar 

  89. Peng L, Wen L, Shi QF, Gao F, Huang B, Meng J, Hu CP, Wang CM (2020) Scutellarin ameliorates pulmonary fibrosis through inhibiting NF-κB/NLRP3-mediated epithelial-mesenchymal transition and inflammation. Cell Death Dis 11(11):978. https://doi.org/10.1038/s41419-020-03178-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Li P, Jin Y, Qi F, Wu F, Luo S, Cheng Y, Montgomery RR, Qian F (2018) SIRT6 acts as a negative regulator in dengue virus-induced inflammatory response by targeting the DNA binding domain of NF-κB p65. Front Cell Infect Microbiol 8:113. https://doi.org/10.3389/fcimb.2018.00113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Mendes KL, Lelis DF, Santos SHS (2017) Nuclear sirtuins and inflammatory signaling pathways. Cytokine Growth Factor Rev 38:98–105. https://doi.org/10.1016/j.cytogfr.2017.11.001

    Article  CAS  PubMed  Google Scholar 

  92. Xiao C, Wang RH, Lahusen TJ, Park O, Bertola A, Maruyama T, Reynolds D, Chen Q, Xu X, Young HA, Chen WJ, Gao B, Deng CX (2012) Progression of chronic liver inflammation and fibrosis driven by activation of c-JUN signaling in Sirt6 mutant mice. J Biol Chem 287(50):41903–41913. https://doi.org/10.1074/jbc.M112.415182

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Hu X, Zhu S, Liu R, Miller JD, Merkley K, Tilton RG, Liu H (2018) Sirt6 deficiency impairs corneal epithelial wound healing. Aging (Albany NY) 10(8):1932–1946. https://doi.org/10.18632/aging.101513

    Article  CAS  Google Scholar 

  94. Liu M, Liang K, Zhen J, Zhou M, Wang X, Wang Z, Wei X, Zhang Y, Sun Y, Zhou Z, Su H, Zhang C, Li N, Gao C, Peng J, Yi F (2017) Sirt6 deficiency exacerbates podocyte injury and proteinuria through targeting Notch signaling. Nat Commun 8(1):413. https://doi.org/10.1038/s41467-017-00498-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Jiang H, Khan S, Wang Y, Charron G, He B, Sebastian C, Du J, Kim R, Ge E, Mostoslavsky R, Hang HC, Hao Q, Lin H (2013) SIRT6 regulates TNF-α secretion through hydrolysis of long-chain fatty acyl lysine. Nature 496(7443):110–113. https://doi.org/10.1038/nature12038

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Sato Y, Yanagita M (2019) Functional heterogeneity of resident fibroblasts in the kidney. Proc Jpn Acad Ser B Phys Biol Sci 95(8):468–478. https://doi.org/10.2183/pjab.95.033

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Ma J, Sanchez-Duffhues G, Goumans MJ, Ten Dijke P (2020) TGF-β-induced endothelial to mesenchymal transition in disease and tissue engineering. Front Cell Dev Biol 8:260. https://doi.org/10.3389/fcell.2020.00260

    Article  PubMed  PubMed Central  Google Scholar 

  98. Alyaseer AAA, de Lima MHS, Braga TT (2020) The role of NLRP3 inflammasome activation in the epithelial to mesenchymal transition process during the fibrosis. Front Immunol 11:883. https://doi.org/10.3389/fimmu.2020.00883

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Xu X, Xu C, Saud SM, Lu X, Liu L, Fang L, Zhang X, Hu J, Li W (2016) Effect of Kuijie granule on the expression of TGF-β/Smads signaling pathway in patients with ulcerative colitis. Evid Based Complement Alternat Med 2016:2601830. https://doi.org/10.1155/2016/2601830

    Article  PubMed  PubMed Central  Google Scholar 

  100. Zhang H, Chen X, Xue P, Ma X, Li J, Zhang J (2021) FN1 promotes chondrocyte differentiation and collagen production via TGF-β/PI3K/Akt pathway in mice with femoral fracture. Gene 769:145253. https://doi.org/10.1016/j.gene.2020.145253

    Article  CAS  PubMed  Google Scholar 

  101. Deng B, Yang W, Wang D, Cheng L, Bu L, Rao J, Zhang J, Xie J, Zhang B (2020) Peptide DR8 suppresses epithelial-to-mesenchymal transition via the TGF-β/MAPK signaling pathway in renal fibrosis. Life Sci 261:118465. https://doi.org/10.1016/j.lfs.2020.11846

    Article  CAS  PubMed  Google Scholar 

  102. Wang S, Wilkes MC, Leof EB, Hirschberg R (2010) Noncanonical TGF-beta pathways, mTORC1 and Abl, in renal interstitial fibrogenesis. Am J Physiol Renal Physiol 298(1):F142–F149. https://doi.org/10.1152/ajprenal.00320.2009

    Article  CAS  PubMed  Google Scholar 

  103. Meng P, Zhu M, Ling X, Zhou L (2020) Wnt signaling in kidney: the initiator or terminator? J Mol Med (Berl) 98(11):1511–1523. https://doi.org/10.1007/s00109-020-01978-9

    Article  Google Scholar 

  104. Zhong X, Huang M, Kim HG, Zhang Y, Chowdhury K, Cai W, Saxena R, Schwabe RF, Liangpunsakul S, Dong XC (2020) SIRT6 protects against liver fibrosis by deacetylation and suppression of SMAD3 in hepatic stellate cells. Cell Mol Gastroenterol Hepatol 10(2):341–364. https://doi.org/10.1016/j.jcmgh.2020.04.005

    Article  PubMed  PubMed Central  Google Scholar 

  105. Han Q, Xie QR, Li F, Cheng Y, Wu T, Zhang Y, Lu X, Wong AST, Sha J, Xia W (2021) Targeted inhibition of SIRT6 via engineered exosomes impairs tumorigenesis and metastasis in prostate cancer. Theranostics 11(13):6526–6541. https://doi.org/10.7150/thno.53886

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Carraway HE, Malkaram SA, Cen Y, Shatnawi A, Fan J, Ali HEA, Abd Elmageed ZY, Buttolph T, Denvir J, Primerano DA, Fandy TE (2020) Activation of SIRT6 by DNA hypomethylating agents and clinical consequences on combination therapy in leukemia. Sci Rep 10(1):10325. https://doi.org/10.1038/s41598-020-67170-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Yu C, Xiong C, Tang J, Hou X, Liu N, Bayliss G, Zhuang S (2021) Histone demethylase JMJD3 protects against renal fibrosis by suppressing TGFβ and Notch signaling and preserving PTEN expression. Theranostics 11(6):2706–2721. https://doi.org/10.7150/thno.48679

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Nasser F, Moussa N, Helmy MW, Haroun M (2021) Dual targeting of Notch and Wnt/β-catenin pathways: Potential approach in triple-negative breast cancer treatment. Naunyn Schmiedebergs Arch Pharmacol 394(3):481–490. https://doi.org/10.1007/s00210-020-01988-x

    Article  CAS  PubMed  Google Scholar 

  109. Thomas MC, Brownlee M, Susztak K, Sharma K, Jandeleit-Dahm KA, Zoungas S, Rossing P, Groop PH, Cooper ME (2015) Diabetic kidney disease. Nat Rev Dis Primers 1:15018. https://doi.org/10.1038/nrdp.2015.18

    Article  PubMed  PubMed Central  Google Scholar 

  110. Ayinde KS, Olaoba OT, Ibrahim B, Lei D, Lu Q, Yin X, Adelusi TI (2020) AMPK allostery: a therapeutic target for the management/treatment of diabetic nephropathy. Life Sci 261:118455. https://doi.org/10.1016/j.lfs.2020.118455

    Article  CAS  PubMed  Google Scholar 

  111. Barrera-Chimal J, Jaisser F (2020) Pathophysiologic mechanisms in diabetic kidney disease: a focus on current and future therapeutic targets. Diabetes Obes Metab 22(Suppl 1):16–31. https://doi.org/10.1111/dom.13969

    Article  CAS  PubMed  Google Scholar 

  112. Matoba K, Takeda Y, Nagai Y, Yokota T, Utsunomiya K, Nishimura R (2020) Targeting redox imbalance as an approach for diabetic kidney disease. Biomedicines 8(2):40. https://doi.org/10.3390/biomedicines8020040

    Article  CAS  PubMed Central  Google Scholar 

  113. Matoba K, Takeda Y, Nagai Y, Kawanami D, Utsunomiya K, Nishimura R (2019) Unraveling the role of inflammation in the pathogenesis of diabetic kidney disease. Int J Mol Sci 20(14):3393. https://doi.org/10.3390/ijms20143393

    Article  CAS  PubMed Central  Google Scholar 

  114. Feng J, Ma Y, Chen Z, Hu J, Yang Q, Ding G (2019) Mitochondrial pyruvate carrier 2 mediates mitochondrial dysfunction and apoptosis in high glucose-treated podocytes. Life Sci 237:116941. https://doi.org/10.1016/j.lfs.2019.116941

    Article  CAS  PubMed  Google Scholar 

  115. Niewczas MA, Pavkov ME, Skupien J, Smiles A, Md Dom ZI, Wilson JM, Park J, Nair V, Schlafly A, Saulnier PJ, Satake E, Simeone CA, Shah H, Qiu C, Looker HC, Fiorina P, Ware CF, Sun JK, Doria A, Kretzler M, Susztak K, Duffin KL, Nelson RG, Krolewski AS (2019) A signature of circulating inflammatory proteins and development of end-stage renal disease in diabetes. Nat Med 25(5):805–813. https://doi.org/10.1038/s41591-019-0415-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Niranjan T, Bielesz B, Gruenwald A, Ponda MP, Kopp JB, Thomas DB, Susztak K (2008) The Notch pathway in podocytes plays a role in the development of glomerular disease. Nat Med 14(3):290–298. https://doi.org/10.1038/nm1731

    Article  CAS  PubMed  Google Scholar 

  117. El Machhour F, Keuylian Z, Kavvadas P, Dussaule JC, Chatziantoniou C (2015) Activation of Notch3 in glomeruli promotes the development of rapidly progressive renal disease. J Am Soc Nephrol 26(7):1561–1575. https://doi.org/10.1681/ASN.2013090968

    Article  CAS  PubMed  Google Scholar 

  118. Waters AM, Wu MY, Huang YW, Liu GY, Holmyard D, Onay T, Jones N, Egan SE, Robinson LA, Piscione TD (2012) Notch promotes dynamin-dependent endocytosis of nephrin. J Am Soc Nephrol 23(1):27–35. https://doi.org/10.1681/ASN.2011010027

    Article  CAS  PubMed  Google Scholar 

  119. Ji L, Chen Y, Wang H, Zhang W, He L, Wu J, Liu Y (2019) Overexpression of Sirt6 promotes M2 macrophage transformation, alleviating renal injury in diabetic nephropathy. Int J Oncol 55(1):103–115. https://doi.org/10.3892/ijo.2019.4800

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Muraoka H, Hasegawa K, Sakamaki Y, Minakuchi H, Kawaguchi T, Yasuda I, Kanda T, Tokuyama H, Wakino S, Itoh H (2019) Role of Nampt-Sirt6 axis in renal proximal tubules in extracellular matrix deposition in diabetic nephropathy. Cell Rep 27(1):199–212. https://doi.org/10.1016/j.celrep.2019.03.024

    Article  CAS  PubMed  Google Scholar 

  121. Govender S, Pfister C, Rayner B, Dyer R, Flint M, Roodt F, Davids J, Nejthardt MB, Swanevelder JL, Chiu E, Cloete E, Koller V, Pretorius T, Fullerton Z, Roos J, Van Zyl R, Biccard BM (2020) A multicentre cross-sectional descriptive study evaluating the cardiovascular risk profile of preoperatively identified patients with hypertension. S Afr Med J 111(11):74–79. https://doi.org/10.7196/SAMJ.2020.v111i1.14640

    Article  CAS  PubMed  Google Scholar 

  122. Mennuni S, Rubattu S, Pierelli G, Tocci G, Fofi C, Volpe M (2014) Hypertension and kidneys: unraveling complex molecular mechanisms underlying hypertensive renal damage. J Hum Hypertens 28(2):74–79. https://doi.org/10.1038/jhh.2013.55

    Article  CAS  PubMed  Google Scholar 

  123. Zhang W, Cheng B, Lu Q, Sheng Y, Sun X, Chen X (2019) Analysis of the correlations of hypertension complicated with or without hypertensive nephropathy with glucose and lipid metabolism, vascular endothelial function, inflammation, oxidative stress and course of disease. Panminerva Med 62(3):180–183. https://doi.org/10.23736/S0031-0808.19.03649-8

    Article  PubMed  Google Scholar 

  124. Guo J, Wang Z, Wu J, Liu M, Li M, Sun Y, Huang W, Li Y, Zhang Y, Tang W, Li X, Zhang C, Hong F, Li N, Nie J, Yi F (2019) Endothelial SIRT6 is vital to prevent hypertension and associated cardiorenal injury through targeting Nkx3.2-GATA5 signaling. Circ Res 124(10):1448–1461. https://doi.org/10.1161/CIRCRESAHA.118.314032

    Article  CAS  PubMed  Google Scholar 

  125. D’Onofrio N, Servillo L, Balestrieri ML (2018) SIRT1 and SIRT6 signaling pathways in cardiovascular disease protection. Antioxid Redox Signal 28(8):711–732. https://doi.org/10.1089/ars.2017.7178

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Cardus A, Uryga AK, Walters G, Erusalimsky JD (2013) SIRT6 protects human endothelial cells from DNA damage, telomere dysfunction, and senescence. Cardiovasc Res 97(3):571–579. https://doi.org/10.1093/cvr/cvs352

    Article  CAS  PubMed  Google Scholar 

  127. Liu Y, Song JW, Lin JY, Miao R, Zhong JC (2020) Roles of MicroRNA-122 in cardiovascular fibrosis and related diseases. Cardiovasc Toxicol 20(5):463–473. https://doi.org/10.1007/s12012-020-09603-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Song JJ, Yang M, Liu Y, Song JW, Wang J, Chi HJ, Liu XY, Zuo K, Yang XC, Zhong JC (2020) MicroRNA-122 aggravates angiotensin II-mediated apoptosis and autophagy imbalance in rat aortic adventitial fibroblasts via the modulation of SIRT6-elabela-ACE2 signaling. Eur J Pharmacol 883:173374. https://doi.org/10.1016/j.ejphar.2020.173374

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Schroth J, Thiemermann C, Henson SM (2020) Senescence and the aging immune system as major drivers of chronic kidney disease. Front Cell Dev Biol 8:564461. https://doi.org/10.3389/fcell.2020.564461

    Article  PubMed  PubMed Central  Google Scholar 

  130. Kitada M, Kume S, Takeda-Watanabe A, Kanasaki K, Koya D (2013) Sirtuins and renal diseases: relationship with aging and diabetic nephropathy. Clin Sci (Lond) 124(3):153–164. https://doi.org/10.1042/CS20120190

    Article  CAS  Google Scholar 

  131. Zhang J, Hansen KM, Pippin JW, Chang AM, Taniguchi Y, Krofft RD, Pickering SG, Liu ZH, Abrass CK, Shankland SJ (2012) De novo expression of podocyte proteins in parietal epithelial cells in experimental aging nephropathy. Am J Physiol Renal Physiol 302(5):F571–F580. https://doi.org/10.1152/ajprenal.00516.2011

    Article  CAS  PubMed  Google Scholar 

  132. Grootaert MOJ, Finigan A, Figg NL, Uryga AK, Bennett MR (2021) SIRT6 protects smooth muscle cells from senescence and reduces atherosclerosis. Circ Res 128(4):474–491. https://doi.org/10.1161/CIRCRESAHA.120.318353

    Article  CAS  PubMed  Google Scholar 

  133. Pillai VB, Samant S, Hund S, Gupta M, Gupta MP (2021) The nuclear sirtuin SIRT6 protects the heart from developing aging-associated myocyte senescence and cardiac hypertrophy. Aging (Albany NY) 13(9):12334–12358. https://doi.org/10.18632/aging.203027

    Article  CAS  Google Scholar 

  134. Zhang N, Li Z, Mu W, Li L, Liang Y, Lu M, Wang Z, Qiu Y, Wang Z (2016) Calorie restriction-induced SIRT6 activation delays aging by suppressing NF-κB signaling. Cell Cycle 15(7):1009–1018. https://doi.org/10.1080/15384101.2016.1152427

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Huang W, Liu H, Zhu S, Woodson M, Liu R, Tilton RG, Miller JD, Zhang W (2017) Sirt6 deficiency results in progression of glomerular injury in the kidney. Aging (Albany NY) 9(3):1069–1083. https://doi.org/10.18632/aging.101214

    Article  CAS  Google Scholar 

  136. Jeh SU, Park JJ, Lee JS, Kim DC, Do J, Lee SW, Choi SM, Hyun JS, Seo DH, Lee C, Kam SC, Chung KH, Hwa JS (2017) Differential expression of the sirtuin family in renal cell carcinoma: Aspects of carcinogenesis and prognostic significance. Urol Oncol 35(12):675–679. https://doi.org/10.1016/j.urolonc.2017.08.016

    Article  CAS  PubMed  Google Scholar 

  137. Ding Y, Wu S, Huo Y, Chen X, Chai L, Wang Y, Wang X, Zhu G, Jiang W (2019) Inhibition of Sirt6 suppresses tumor growth by inducing G1/S phase arrest in renal cancer cells. Int J Clin Exp Pathol 12(7):2526–2535

    CAS  PubMed  PubMed Central  Google Scholar 

  138. Tan Y, Li B, Peng F, Gong G, Li N (2020) Integrative analysis of sirtuins and their prognostic significance in clear cell renal cell carcinoma. Front Oncol 10:218. https://doi.org/10.3389/fonc.2020.00218

    Article  PubMed  PubMed Central  Google Scholar 

  139. An J, Yang J, Yao Y, Lu K, Zhao Z, Yu M, Zhu Y (2021) Sirtuin 6 regulates the proliferation and survival of clear cell renal cell carcinoma cells via B-cell lymphoma 2. Oncol Lett 21(4):293. https://doi.org/10.3892/ol.2021.12554

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Ren H, Zuo S, Hou Y, Shang W, Liu N, Yin Z (2020) Inhibition of α1-adrenoceptor reduces TGF-β1-induced epithelial-to-mesenchymal transition and attenuates UUO-induced renal fibrosis in mice. FASEB J 34(11):14892–14904. https://doi.org/10.1096/fj.202000737RRR

    Article  CAS  PubMed  Google Scholar 

  141. Wetzel MD, Stanley K, Wang WW, Maity S, Awad AS (2020) Selective inhibition of arginase-2 in endothelial cells but not proximal tubules reduces renal fibrosis. JCI Insight 5(19):e142187. https://doi.org/10.1172/jci.insight.142187

    Article  PubMed Central  Google Scholar 

  142. Li X, Pan J, Li H, Li G, Liu X, Liu B, He Z, Peng Z, Zhang H, Li Y, Xiang X, Chai X, Yuan Y, Zheng P, Liu F, Zhang D (2020) DsbA-L mediated renal tubulointerstitial fibrosis in UUO mice. Nat Commun 11(1):4467. https://doi.org/10.1038/s41467-020-18304-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Wyczanska M, Lange-Sperandio B (2020) DAMPs in unilateral ureteral obstruction. Front Immunol 11:581300. https://doi.org/10.3389/fimmu.2020.581300

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. You YK, Luo Q, Wu WF, Zhang JJ, Zhu HJ, Lao L, Lan HY, Chen HY, Cheng YX (2019) Petchiether A attenuates obstructive nephropathy by suppressing TGF-β/Smad3 and NF-κB signalling. J Cell Mol Med 23(8):5576–5587. https://doi.org/10.1111/jcmm.14454

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Martínez-Klimova E, Aparicio-Trejo OE, Gómez-Sierra T, Jiménez-Uribe AP, Bellido B, Pedraza-Chaverri J (2020) Mitochondrial dysfunction and endoplasmic reticulum stress in the promotion of fibrosis in obstructive nephropathy induced by unilateral ureteral obstruction. BioFactors 46(5):716–733. https://doi.org/10.1002/biof.1673

    Article  CAS  PubMed  Google Scholar 

  146. Duan Z, Cai G, Li J, Chen X (2020) Cisplatin-induced renal toxicity in elderly people. Ther Adv Med Oncol 12:1758835920923430. https://doi.org/10.1177/1758835920923430

    Article  PubMed  PubMed Central  Google Scholar 

  147. Crona DJ, Faso A, Nishijima TF, McGraw KA, Galsky MD, Milowsky MI (2017) A systematic review of strategies to prevent cisplatin-Induced nephrotoxicity. Oncologist 22(5):609–619. https://doi.org/10.1634/theoncologist.2016-0319

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Wang H, Xia W, Long G, Pei Z, Li Y, Wu M, Wang Q, Zhang Y, Jia Z, Chen H (2020) Isoquercitrin ameliorates cisplatin-induced nephrotoxicity the inhibition of apoptosis, inflammation, and oxidative stress. Front Pharmacol 11:599416. https://doi.org/10.3389/fphar.2020.599416

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Zhang Y, Chen Y, Li B, Ding P, Jin D, Hou S, Cai X, Sheng X (2020) The effect of monotropein on alleviating cisplatin-induced acute kidney injury by inhibiting oxidative damage, inflammation and apoptosis. Biomed Pharmacother 129:110408. https://doi.org/10.1016/j.biopha.2020.110408

    Article  CAS  PubMed  Google Scholar 

  150. Fan X, Wei W, Huang J, Peng L, Ci X (2020) Daphnetin attenuated cisplatin-induced acute nephrotoxicity with enhancing antitumor activity of cisplatin by upregulating SIRT1/SIRT6-Nrf2 pathway. Front Pharmacol 11:579178. https://doi.org/10.3389/fphar.2020.579178

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Li Z, Xu K, Zhang N, Amador G, Wang Y, Zhao S, Li L, Qiu Y, Wang Z (2018) Overexpressed SIRT6 attenuates cisplatin-induced acute kidney injury by inhibiting ERK1/2 signaling. Kidney Int 93(4):881–892. https://doi.org/10.1016/j.kint.2017.10.021

    Article  CAS  PubMed  Google Scholar 

  152. Nadeem A, Ahmad SF, Al-Harbi NO, Ibrahim KE, Alqahtani F, Alanazi WA, Mahmood HM, Alsanea S, Attia SM (2021) Bruton’s tyrosine kinase inhibition attenuates oxidative stress in systemic immune cells and renal compartment during sepsis-induced acute kidney injury in mice. Int Immunopharmacol 90:107123. https://doi.org/10.1016/j.intimp.2020.107123

    Article  CAS  PubMed  Google Scholar 

  153. Zhang Y, Wang L, Meng L, Cao G, Wu Y (2019) Sirtuin 6 overexpression relieves sepsis-induced acute kidney injury by promoting autophagy. Cell Cycle 18(4):425–436. https://doi.org/10.1080/15384101.2019.1568746

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Luo T, Yuan Y, Yu Q, Liu G, Long M, Zhang K, Bian J, Gu J, Zou H, Wang Y, Zhu J, Liu X, Liu Z (2017) PARP-1 overexpression contributes to Cadmium-induced death in rat proximal tubular cells via parthanatos and the MAPK signalling pathway. Sci Rep 7(1):4331. https://doi.org/10.1038/s41598-017-04555-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. So KY, Park BH, Oh SH (2020) Cytoplasmic sirtuin 6 translocation mediated by p62 polyubiquitination plays a critical role in cadmium-induced kidney toxicity. Cell Biol Toxicol 37(2):193–207. https://doi.org/10.1007/s10565-020-09528-2

    Article  CAS  PubMed  Google Scholar 

  156. Yuan X, Chen G, Guo D, Xu L, Gu Y (2020) Polydatin alleviates septic myocardial injury by promoting SIRT6-mediated autophagy. Inflammation 43(3):785–795. https://doi.org/10.1007/s10753-019-01153-4

    Article  CAS  PubMed  Google Scholar 

  157. Li Y, Liu M, Song X, Zheng X, Yi J, Liu D, Wang S, Chu C, Yang J (2020) Exogenous hydrogen sulfide ameliorates diabetic myocardial fibrosis by inhibiting cell aging through SIRT6/AMPK autophagy. Front Pharmacol 11:1150. https://doi.org/10.3389/fphar.2020.01150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Basile DP, Donohoe D, Roethe K, Osborn JL (2001) Renal ischemic injury results in permanent damage to peritubular capillaries and influences long-term function. Am J Physiol Renal Physiol 281(5):F887–F899. https://doi.org/10.1152/ajprenal.2001.281.5.F887

    Article  CAS  PubMed  Google Scholar 

  159. Tammaro A, Kers J, Scantlebery AML, Florquin S (2020) Metabolic flexibility and innate immunity in renal ischemia reperfusion injury: the fine balance between adaptive repair and tissue degeneration. Front Immunol 11:1346. https://doi.org/10.3389/fimmu.2020.01346

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Arshad A, Ayaz A, Rehman S, Ukrani RD, Akbar I, Jamil B (2020) Progression of acute kidney injury to chronic kidney disease in sepsis survivors: 1-year follow-up study. J Intensive Care Med 36(11):1366–1370. https://doi.org/10.1177/0885066620956621

    Article  PubMed  Google Scholar 

  161. Kruger C, Nguyen TT, Breaux C, Guillory A, Mangelli M, Fridianto KT, Kovalik JP, Burk DH, Noland RC, Mynatt R, Stadler K (2019) Proximal tubular cell-specific ablation of carnitine acetyltransferase causes tubular disease and secondary glomerulosclerosis. Diabetes 68(4):819–831. https://doi.org/10.2337/db18-0090

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Console L, Scalise M, Giangregorio N, Tonazzi A, Barile M, Indiveri C (2020) The link between the mitochondrial fatty acid oxidation derangement and kidney injury. Front Physiol 11:794. https://doi.org/10.3389/fphys.2020.00794

    Article  PubMed  PubMed Central  Google Scholar 

  163. Liu R, Wang SC, Li M, Ma XH, Jia XN, Bu Y, Sun L, Yu KJ (2020) An inhibitor of DRP1 (Mdivi-1) alleviates LPS-induced septic AKI by inhibiting NLRP3 inflammasome activation. Biomed Res Int 2020:2398420. https://doi.org/10.1155/2020/2398420

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Ullah MM, Basile DP (2019) Role of renal hypoxia in the progression from acute kidney injury to chronic kidney disease. Semin Nephrol 39(6):567–580. https://doi.org/10.1016/j.semnephrol.2019.10.006

    Article  PubMed  PubMed Central  Google Scholar 

  165. Liao W, Liang P, Liu B, Xu Z, Zhang L, Feng M, Tang Y, Xu A (2020) MicroRNA-140-5p mediates renal fibrosis through TGF-β1/Smad signaling pathway by directly targeting TGFBR1. Front Physiol 11:1093. https://doi.org/10.3389/fphys.2020.01093

    Article  PubMed  PubMed Central  Google Scholar 

  166. Coca SG, Yusuf B, Shlipak MG, Garg AX, Parikh CR (2009) Long-term risk of mortality and other adverse outcomes after acute kidney injury: a systematic review and meta-analysis. Am J Kidney Dis 53(6):961–973. https://doi.org/10.1053/j.ajkd.2008.11.034

    Article  PubMed  PubMed Central  Google Scholar 

  167. Mitra K, Wunder C, Roysam B, Lin G, Lippincott-Schwartz J (2009) A hyperfused mitochondrial state achieved at G1-S regulates cyclin E buildup and entry into S phase. Proc Natl Acad Sci USA 106(29):11960–11965. https://doi.org/10.1073/pnas.0904875106

    Article  PubMed  PubMed Central  Google Scholar 

  168. Lok SWY, Yiu WH, Li H, Xue R, Zou Y, Li B, Chan KW, Chan LYY, Leung JCK, Lai KN, Tang SCW (2020) The PAR-1 antagonist vorapaxar ameliorates kidney injury and tubulointerstitial fibrosis. Clin Sci (Lond) 134(21):2873–2891. https://doi.org/10.1042/CS20200923

    Article  Google Scholar 

  169. Liang Y, Liang L, Liu Z, Wang Y, Dong X, Qu L, Gou R, Wang Y, Wang Q, Liu Z, Tang L (2020) Inhibition of IRE1/JNK pathway in HK-2 cells subjected to hypoxia-reoxygenation attenuates mesangial cells-derived extracellular matrix production. J Cell Mol Med 24(22):13408–13420. https://doi.org/10.1111/jcmm.15964

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Ke Q, Yuan Q, Qin N, Shi C, Luo J, Fang Y, Xu L, Sun Q, Zen K, Jiang L, Zhou Y, Yang J (2020) UCP2-induced hypoxia promotes lipid accumulation and tubulointerstitial fibrosis during ischemic kidney injury. Cell Death Dis 11(1):26. https://doi.org/10.1038/s41419-019-2219-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. Zhang L, Liu L, Bai M, Liu M, Wei L, Yang Z, Qian Q, Ning X, Sun S (2020) Hypoxia-induced HE4 in tubular epithelial cells promotes extracellular matrix accumulation and renal fibrosis via NF-κB. FASEB J 34(2):2554–2567. https://doi.org/10.1096/fj.201901950R

    Article  CAS  PubMed  Google Scholar 

  172. Gao Z, Chen X, Fan Y, Zhu K, Shi M, Ding G (2020) Sirt6 attenuates hypoxia-induced tubular epithelial cell injury via targeting G2/M phase arrest. J Cell Physiol 235(4):3463–3473. https://doi.org/10.1002/jcp.29235

    Article  CAS  PubMed  Google Scholar 

  173. Tang C, Cai J, Yin XM, Weinberg JM, Venkatachalam MA, Dong Z (2021) Mitochondrial quality control in kidney injury and repair. Nat Rev Nephrol 17(5):299–318. https://doi.org/10.1038/s41581-020-00369-0

    Article  CAS  PubMed  Google Scholar 

  174. Murata H, Takamatsu H, Liu S, Kataoka K, Huh NH, Sakaguchi M (2015) NRF2 regulates PINK1 expression under oxidative stress conditions. PLoS ONE 10(11):e142438. https://doi.org/10.1371/journal.pone.0142438

    Article  CAS  Google Scholar 

  175. Yu LM, Dong X, Xue XD, Xu S, Zhang X, Xu YL, Wang ZS, Wang Y, Gao H, Liang YX, Yang Y, Wang HS (2021) Melatonin attenuates diabetic cardiomyopathy and reduces myocardial vulnerability to ischemia-reperfusion injury by improving mitochondrial quality control: role of SIRT6. J Pineal Res 70(1):e12698. https://doi.org/10.1111/jpi.12698

    Article  CAS  PubMed  Google Scholar 

  176. Iachettini S, Trisciuoglio D, Rotili D, Lucidi A, Salvati E, Zizza P, Di Leo L, Del Bufalo D, Ciriolo MR, Leonetti C, Steegborn C, Mai A, Rizzo A, Biroccio A (2018) Pharmacological activation of SIRT6 triggers lethal autophagy in human cancer cells. Cell Death Dis 9(10):996. https://doi.org/10.1038/s41419-018-1065-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Cases A, Coll E (2005) Dyslipidemia and the progression of renal disease in chronic renal failure patients. Kidney Int Suppl. https://doi.org/10.1111/j.1523-1755.2005.09916.x

    Article  PubMed  Google Scholar 

  178. Kang HM, Ahn SH, Choi P, Ko YA, Han SH, Chinga F, Park AS, Tao J, Sharma K, Pullman J, Bottinger EP, Goldberg IJ, Susztak K (2015) Defective fatty acid oxidation in renal tubular epithelial cells has a key role in kidney fibrosis development. Nat Med 21(1):37–46. https://doi.org/10.1038/nm.3762

    Article  CAS  PubMed  Google Scholar 

  179. Chen Q, Hao W, Xiao C, Wang R, Xu X, Lu H, Chen W, Deng CX (2017) SIRT6 is essential for adipocyte differentiation by regulating mitotic clonal expansion. Cell Rep 18(13):3155–3166. https://doi.org/10.1016/j.celrep.2017.03.006

    Article  CAS  PubMed  Google Scholar 

  180. D’Onofrio N, Pieretti G, Ciccarelli F, Gambardella A, Passariello N, Rizzo MR, Barbieri M, Marfella R, Nicoletti G, Balestrieri ML, Sardu C (2019) Abdominal fat SIRT6 expression and Its relationship with inflammatory and metabolic pathways in pre-diabetic overweight patients. Int J Mol Sci 20(5):1153. https://doi.org/10.3390/ijms20051153

    Article  CAS  PubMed Central  Google Scholar 

  181. Yang F, Huang XR, Chung AC, Hou CC, Lai KN, Lan HY (2010) Essential role for Smad3 in angiotensin II-induced tubular epithelial-mesenchymal transition. J Pathol 221(4):390–401. https://doi.org/10.1002/path.2721

    Article  CAS  PubMed  Google Scholar 

  182. Hassan NME, Said E, Shehatou GSG (2021) Nifuroxazide suppresses UUO-induced renal fibrosis in rats via inhibiting STAT-3/NF-κB signaling, oxidative stress and inflammation. Life Sci 272:119241. https://doi.org/10.1016/j.lfs.2021.119241

    Article  CAS  PubMed  Google Scholar 

  183. Lu A, Pallero MA, Owusu BY, Borovjagin AV, Lei W, Sanders PW, Murphy-Ullrich JE (2020) Calreticulin is important for the development of renal fibrosis and dysfunction in diabetic nephropathy. Matrix Biol Plus 8:100034. https://doi.org/10.1016/j.mbplus.2020.100034

    Article  PubMed  PubMed Central  Google Scholar 

  184. Zhou D, Li Y, Lin L, Zhou L, Igarashi P, Liu Y (2012) Tubule-specific ablation of endogenous β-catenin aggravates acute kidney injury in mice. Kidney Int 82(5):537–547. https://doi.org/10.1038/ki.2012.173

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  185. Bielesz B, Sirin Y, Si H, Niranjan T, Gruenwald A, Ahn S, Kato H, Pullman J, Gessler M, Haase VH, Susztak K (2010) Epithelial Notch signaling regulates interstitial fibrosis development in the kidneys of mice and humans. J Clin Invest 120(11):4040–4054. https://doi.org/10.1172/JCI430254

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This study was supported by the Grants from National Natural Science Foundation of China (No. 81770687 and 82070713 to G.D., 81970631 to W.L., and 81670631 to D.Y.).

Author information

Author notes

  1. Xueyan Yang and Jun Feng are co-first authors.

Authors and Affiliations

  1. Division of Nephrology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, China

    Xueyan Yang, Jun Feng, Wei Liang, Zijing Zhu, Zhaowei Chen, Jijia Hu, Dingping Yang & Guohua Ding

  2. Nephrology and Urology Research Institute of Wuhan University, Wuhan, Hubei, China

    Xueyan Yang, Jun Feng, Wei Liang, Zijing Zhu, Zhaowei Chen, Jijia Hu, Dingping Yang & Guohua Ding

Authors
  1. Xueyan Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jun Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wei Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zijing Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zhaowei Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jijia Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Dingping Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Guohua Ding
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

XY, JF, WL, DY, and GD put forward the concept. XY and JF performed a review of article and wrote the manuscript. ZZ, ZC, and JH contributed to language modification and content adjustment. XY, JF, WL, and GD participated in the revision of this manuscript. All authors have read the article and approved the final version.

Corresponding author

Correspondence to Guohua Ding.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yang, X., Feng, J., Liang, W. et al. Roles of SIRT6 in kidney disease: a novel therapeutic target. Cell. Mol. Life Sci. 79, 53 (2022). https://doi.org/10.1007/s00018-021-04061-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00018-021-04061-9

Keywords

Search

Navigation