Skip to main content
SpringerLink
Log in

Mechanism of progression of diabetic kidney disease mediated by podocyte mitochondrial injury

  • Review
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Diabetic kidney disease (DKD) is an important diabetic microvascular complication, which has become the main cause of end-stage renal disease (ESRD) all over the world. It is of great significance to find effective therapeutic targets and improve the prognosis of the disease. Traditionally, it is believed that the activation of the renin–angiotensin–aldosterone system (RAAS) is the main reason for the progression of DKD, but with the progress of research, it is known that the production of proteinuria in patients with DKD is also related to podocyte injury and loss. Many studies have shown that mitochondrial dysfunction in podocytes plays an important role in the occurrence and development of DKD, and oxidative stress is also the main pathway and common hub of diabetes to the occurrence and development of microvascular and macrovascular complications. Thus, the occurrence and progression of DKD is correlated with not only the activation of the RAAS, but also the damage of mitochondria, oxidative stress, and inflammatory mediators. Besides, diabetes-related metabolic disorders can also cause abnormalities in mitochondrial dynamics, autophagy and cellular signal transduction, which are intertwined in a complex way. Therefore, in this review, we mainly explore the mechanism and the latest research progress of podocyte mitochondria in DKD and summarize the main signal pathways involved in them. Thus, it provides feasible clinical application and future research suggestions for the prevention and treatment of DKD, which has important practical significance for the later treatment of patients with DKD.

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

Similar content being viewed by others

References

  1. Lindblom R, Higgins G, Coughlan M, de Haan JB (2015) Targeting mitochondria and reactive oxygen species-driven pathogenesis in diabetic nephropathy. Rev Diabet Stud 12(1–2):134–156. https://doi.org/10.1900/RDS.2015.12.134

    Article  PubMed  PubMed Central  Google Scholar 

  2. Schiffer TA, Friederich-Persson M (2017) Mitochondrial reactive oxygen species and kidney hypoxia in the development of diabetic nephropathy. Front Physiol 8:211. https://doi.org/10.3389/fphys.2017.00211

    Article  PubMed  PubMed Central  Google Scholar 

  3. Lewis KUJB (2018) Update on diabetic nephropathy: core curriculum 2018. Am J Kidney Dis 71(6):884–895. https://doi.org/10.1053/j.ajkd.2017.10.026

    Article  PubMed  Google Scholar 

  4. Sagoo MK, Gnudi L (2018) Diabetic nephropathy: is there a role for oxidative stress? Free Radic Biol Med 116:50–63. https://doi.org/10.1016/j.freeradbiomed.2017.12.040

    Article  CAS  PubMed  Google Scholar 

  5. Ling-Feng Z, Xiao Y, Sun L (2019) A glimpse of the mechanisms related to renal fibrosis in diabetic nephropathy. Adv Exp Med Biol 1165:49–79

    Article  Google Scholar 

  6. Bose M, Almas S, Prabhakar S (2017) Wnt signaling and podocyte dysfunction in diabetic nephropathy. J Investig Med 65(8):1093–1101. https://doi.org/10.1136/jim-2017-000456

    Article  PubMed  Google Scholar 

  7. Imasawa T, Obre E, Bellance N, Lavie J, Imasawa T, Rigothier C et al (2017) High glucose repatterns human podocyte energy metabolism during differentiation and diabetic nephropathy. FASEB J 31(1):294–307. https://doi.org/10.1096/fj.201600293R

    Article  CAS  PubMed  Google Scholar 

  8. Dai H, Liu Q, Liu B (2017) Research progress on mechanism of podocyte depletion in diabetic nephropathy. J Diabetes Res 2017:1–10. https://doi.org/10.1155/2017/2615286

    Article  CAS  Google Scholar 

  9. Rodewald R, Karnovsky MJ (1974) Porous substructure of the glomerular slit diaphragm in the rat and mouse. J Cell Biol 60(2):423–433

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Grahammer F, Wigge C, Schell C, Kretz O, Patrakka J, Schneider S et al (2016) A flexible, multilayered protein scaffold maintains the slit in between glomerular podocytes. JCI Insight. https://doi.org/10.1172/jci.insight.86177

    Article  PubMed  PubMed Central  Google Scholar 

  11. Nagata M (2016) Podocyte injury and its consequences. Kidney Int 89(6):1221–1230. https://doi.org/10.1016/j.kint.2016.01.012

    Article  CAS  PubMed  Google Scholar 

  12. Parikh SM, Yang Y, He L, Tang C, Zhan M, Dong Z (2015) Mitochondrial function and disturbances in the septic kidney. Semin Nephrol 35(1):108–119. https://doi.org/10.1016/j.semnephrol.2015.01.011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Sharma K (2017) Mitochondrial dysfunction in the diabetic kidney. Adv Exp Med Biol 982:553–562. https://doi.org/10.1007/978-3-319-55330-6_28

    Article  CAS  PubMed  Google Scholar 

  14. Lee SY, Choi ME (2015) Urinary biomarkers for early diabetic nephropathy: beyond albuminuria. Pediatr Nephrol 30(7):1063–1075. https://doi.org/10.1007/s00467-014-2888-2

    Article  PubMed  Google Scholar 

  15. Liu M, Liang K, Zhen J, Zhou M, Wang X, Wang Z et al (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 

  16. Tung CW, Hsu YC, Shih YH, Chang PJ, Lin CL (2018) Glomerular mesangial cell and podocyte injuries in diabetic nephropathy. Nephrology (Carlton, Vic) 23(Suppl 4):32–37. https://doi.org/10.1111/nep.13451

    Article  CAS  Google Scholar 

  17. Coward R, Fornoni A (2015) Insulin signaling: implications for podocyte biology in diabetic kidney disease. Curr Opin Nephrol Hypertens 24(1):104–110. https://doi.org/10.1097/MNH.0000000000000078

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Thomas MC, Brownlee M, Susztak K, Sharma K, Jandeleit-Dahm KA, Zoungas S et al (2015) Diabetic kidney disease. Nat Rev Dis Primers 1:15018. https://doi.org/10.1038/nrdp.2015.18

    Article  PubMed  PubMed Central  Google Scholar 

  19. Lin F, Bao Y-W, Wu F-G (2018) Improving the phototherapeutic efficiencies of molecular and nanoscale materials by targeting mitochondria. Molecules. https://doi.org/10.3390/molecules23113016

    Article  PubMed  PubMed Central  Google Scholar 

  20. Flemming NB, Gallo LA, Forbes JM (2018) Mitochondrial dysfunction and signaling in diabetic kidney disease: oxidative stress and beyond. Semin Nephrol 38(2):101–110. https://doi.org/10.1016/j.semnephrol.2018.01.001

    Article  CAS  PubMed  Google Scholar 

  21. Forbes JM, Thorburn DR (2018) Mitochondrial dysfunction in diabetic kidney disease. Nat Rev Nephrol 14(5):291–312. https://doi.org/10.1038/nrneph.2018.9

    Article  CAS  PubMed  Google Scholar 

  22. Hamanaka RB, Chandel NS (2010) Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes. Trends Biochem Sci 35(9):505–513. https://doi.org/10.1016/j.tibs.2010.04.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Cross CE, Halliwell B, Borish ET, Pryor WA, Ames BN, Saul RL et al (1987) Oxygen radicals and human disease. Ann Intern Med 107(4):526–545

    Article  CAS  PubMed  Google Scholar 

  24. Rhee SG (2006) Cell signaling. H2O2, a necessary evil for cell signaling. Science 312(5782):1882–1883

    Article  PubMed  Google Scholar 

  25. Murphy MP (2009) How mitochondria produce reactive oxygen species. Biochem J. https://doi.org/10.1042/BJ20081386

    Article  PubMed  Google Scholar 

  26. Quinlan CL, Perevoshchikova IV, Hey-Mogensen M, Orr AL, Brand MD (2013) Sites of reactive oxygen species generation by mitochondria oxidizing different substrates. Redox Biol 1:304–312. https://doi.org/10.1016/j.redox.2013.04.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Nickel A, Kohlhaas M, Maack C (2014) Mitochondrial reactive oxygen species production and elimination. J Mol Cell Cardiol 73:26–33. https://doi.org/10.1016/j.yjmcc.2014.03.011

    Article  CAS  PubMed  Google Scholar 

  28. Turrens JF (2003) Mitochondrial formation of reactive oxygen species. J Physiol (Lond) 552(Pt 2):335–344

    Article  CAS  Google Scholar 

  29. Fridovich I (1997) Superoxide anion radical (O2−·), superoxide dismutases, and related matters. J Biol Chem 272(30):18515–18517

    Article  CAS  PubMed  Google Scholar 

  30. Holmström KM, Finkel T (2014) Cellular mechanisms and physiological consequences of redox-dependent signalling. Nat Rev Mol Cell Biol 15(6):411–421. https://doi.org/10.1038/nrm3801

    Article  CAS  PubMed  Google Scholar 

  31. Chandel NS (2015) Evolution of mitochondria as signaling organelles. Cell Metab 22(2):204–206. https://doi.org/10.1016/j.cmet.2015.05.013

    Article  CAS  PubMed  Google Scholar 

  32. Yang S, Han Y, Liu J, Song P, Xu X, Zhao L et al (2017) Mitochondria: a novel therapeutic target in diabetic nephropathy. Curr Med Chem 24(29):3185–3202. https://doi.org/10.2174/0929867324666170509121003

    Article  CAS  PubMed  Google Scholar 

  33. Jha JC, Banal C, Chow BSM, Cooper ME, Jandeleit-Dahm K (2016) Diabetes and kidney disease: role of oxidative stress. Antioxid Redox Signal 25(12):657–684

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Nishikawa T, Brownlee M, Araki E (2015) Mitochondrial reactive oxygen species in the pathogenesis of early diabetic nephropathy. J Diabetes Investig 6(2):137–139. https://doi.org/10.1111/jdi.12258

    Article  CAS  PubMed  Google Scholar 

  35. Jha JC, Ho F, Dan C, Jandeleit-Dahm K (2018) A causal link between oxidative stress and inflammation in cardiovascular and renal complications of diabetes. Clin Sci (Lond, Engl, 1979). 132(16):1811–1836. https://doi.org/10.1042/cs20171459

    Article  CAS  Google Scholar 

  36. Bargiela D, Burr SP, Chinnery PF (2018) Mitochondria and hypoxia: metabolic crosstalk in cell-fate decisions. Trends Endocrinol Metab 29(4):249–259. https://doi.org/10.1016/j.tem.2018.02.002

    Article  CAS  PubMed  Google Scholar 

  37. Herr CQ, Hausinger RP (2018) Amazing diversity in biochemical roles of Fe(II)/2-oxoglutarate oxygenases. Trends Biochem Sci 43(7):517–532. https://doi.org/10.1016/j.tibs.2018.04.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Fuhrmann DC, Brune B (2017) Mitochondrial composition and function under the control of hypoxia. Redox Biol 12:208–215. https://doi.org/10.1016/j.redox.2017.02.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Thomas JL, Pham H, Li Y, Hall E, Perkins GA, Ali SS et al (2017) Hypoxia-inducible factor-1α activation improves renal oxygenation and mitochondrial function in early chronic kidney disease. Am J Physiol Renal Physiol 313(2):F282–F290. https://doi.org/10.1152/ajprenal.00579.2016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Nordquist L, Friederich-Persson M, Fasching A, Liss P, Shoji K, Nangaku M et al (2015) Activation of hypoxia-inducible factors prevents diabetic nephropathy. J Am Soc Nephrol JASN 26(2):328–338. https://doi.org/10.1681/ASN.2013090990

    Article  CAS  PubMed  Google Scholar 

  41. Persson P, Palm F (2017) Hypoxia-inducible factor activation in diabetic kidney disease. Curr Opin Nephrol Hypertens 26(5):345–350. https://doi.org/10.1097/MNH.0000000000000341

    Article  CAS  PubMed  Google Scholar 

  42. Mizushima N, Yoshimori T, Ohsumi Y (2011) The role of Atg proteins in autophagosome formation. Annu Rev Cell Dev Biol 27:107–132. https://doi.org/10.1146/annurev-cellbio-092910-154005

    Article  CAS  PubMed  Google Scholar 

  43. Wang P, Mugume Y, Bassham DC (2018) New advances in autophagy in plants: regulation, selectivity and function. Semin Cell Dev Biol 80:113–122. https://doi.org/10.1016/j.semcdb.2017.07.018

    Article  CAS  PubMed  Google Scholar 

  44. Randow F, Youle RJ (2014) Self and nonself: how autophagy targets mitochondria and bacteria. Cell Host Microbe 15(4):403–411. https://doi.org/10.1016/j.chom.2014.03.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Maejima I, Takahashi A, Omori H, Kimura T, Takabatake Y, Saitoh T et al (2013) Autophagy sequesters damaged lysosomes to control lysosomal biogenesis and kidney injury. EMBO J 32(17):2336–2347. https://doi.org/10.1038/emboj.2013.171

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Duan WJ, Li YF, Liu FL, Deng J, Wu YP, Yuan WL et al (2016) A SIRT3/AMPK/autophagy network orchestrates the protective effects of trans-resveratrol in stressed peritoneal macrophages and RAW 264.7 macrophages. Free Radic Biol Med 95:230–242. https://doi.org/10.1016/j.freeradbiomed.2016.03.022

    Article  CAS  PubMed  Google Scholar 

  47. Roy S, Kim D, Sankaramoorthy A (2019) Mitochondrial structural changes in the pathogenesis of diabetic retinopathy. J Clin Med. https://doi.org/10.3390/jcm8091363

    Article  PubMed  PubMed Central  Google Scholar 

  48. Zhao Y, Guo Y, Jiang Y, Zhu X, Liu Y, Zhang X (2017) Mitophagy regulates macrophage phenotype in diabetic nephropathy rats. Biochem Biophys Res Commun 494(1–2):42–50

    Article  CAS  PubMed  Google Scholar 

  49. Ding Y, Choi ME (2015) Autophagy in diabetic nephropathy. J Endocrinol 224(1):R15–R30. https://doi.org/10.1530/JOE-14-0437

    Article  CAS  PubMed  Google Scholar 

  50. Smith MA, Covington MD, Schnellmann RG (2012) Loss of calpain 10 causes mitochondrial dysfunction during chronic hyperglycemia. Arch Biochem Biophys 523(2):161–168. https://doi.org/10.1016/j.abb.2012.04.020

    Article  CAS  PubMed  Google Scholar 

  51. Zhan M, Usman IM, Sun L, Kanwar YS (2015) Disruption of renal tubular mitochondrial quality control by Myo-inositol oxygenase in diabetic kidney disease. J Am Soc Nephrol JASN 26(6):1304–1321. https://doi.org/10.1681/ASN.2014050457

    Article  CAS  PubMed  Google Scholar 

  52. Higgins GC, Coughlan MT (2014) Mitochondrial dysfunction and mitophagy: the beginning and end to diabetic nephropathy? Br J Pharmacol 171(8):1917–1942. https://doi.org/10.1111/bph.12503

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Long J, Badal SS, Ye Z, Wang Y, Ayanga BA, Galvan DL et al (2016) Long noncoding RNA Tug1 regulates mitochondrial bioenergetics in diabetic nephropathy. J Clin Investig 126(11):4205–4218. https://doi.org/10.1172/JCI87927

    Article  PubMed  PubMed Central  Google Scholar 

  54. Kasashima K, Sumitani M, Satoh M, Endo H (2008) Human prohibitin 1 maintains the organization and stability of the mitochondrial nucleoids. Exp Cell Res 314(5):988–996. https://doi.org/10.1016/j.yexcr.2008.01.005

    Article  CAS  PubMed  Google Scholar 

  55. Merkwirth C, Martinelli P, Korwitz A, Morbin M, Brönneke HS, Jordan SD et al (2012) Loss of prohibitin membrane scaffolds impairs mitochondrial architecture and leads to tau hyperphosphorylation and neurodegeneration. PLoS Genet 8(11):e1003021. https://doi.org/10.1371/journal.pgen.1003021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Ising C, Koehler S, Brähler S, Merkwirth C, Höhne M, Baris OR et al (2015) Inhibition of insulin/IGF-1 receptor signaling protects from mitochondria-mediated kidney failure. EMBO Mol Med 7(3):275–287. https://doi.org/10.15252/emmm.201404916

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Mallipattu SK, Horne SJ, D'Agati V, Narla G, Liu R, Frohman MA et al (2015) Krüppel-like factor 6 regulates mitochondrial function in the kidney. J Clin Investig 125(3):1347–1361. https://doi.org/10.1172/JCI77084

    Article  PubMed  PubMed Central  Google Scholar 

  58. Horne SJ, Vasquez JM, Guo Y, Ly V, Piret SE, Leonardo AR et al (2018) Podocyte-specific loss of Kruppel-like factor 6 increases mitochondrial injury in diabetic kidney disease. Diabetes 67(11):2420–2433. https://doi.org/10.2337/db17-0958

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Ducasa GM, Mitrofanova A, Mallela SK, Liu X, Molina J, Sloan A et al (2019) ATP-binding cassette A1 deficiency causes cardiolipin-driven mitochondrial dysfunction in podocytes. J Clin Invest 129(8):3387–3400. https://doi.org/10.1172/JCI125316

    Article  PubMed  PubMed Central  Google Scholar 

  60. Herman-Edelstein M, Scherzer P, Tobar A, Levi M, Gafter U (2014) Altered renal lipid metabolism and renal lipid accumulation in human diabetic nephropathy. J Lipid Res 55(3):561–572. https://doi.org/10.1194/jlr.P040501

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Wang N, Silver DL, Thiele C, Tall AR (2001) ATP-binding cassette transporter A1 (ABCA1) functions as a cholesterol efflux regulatory protein. J Biol Chem 276(26):23742–23747

    Article  CAS  PubMed  Google Scholar 

  62. Paradies G, Paradies V, De Benedictis V, Ruggiero FM, Petrosillo G (2014) Functional role of cardiolipin in mitochondrial bioenergetics. Biochim Biophys Acta 1837(4):408–417. https://doi.org/10.1016/j.bbabio.2013.10.006

    Article  CAS  PubMed  Google Scholar 

  63. Kawanami D, Matoba K, Utsunomiya K (2016) Signaling pathways in diabetic nephropathy. Histol Histopathol 31(10):1059–1067. https://doi.org/10.14670/hh-11-777

    Article  CAS  PubMed  Google Scholar 

  64. Kubota N, Yano W, Kubota T, Yamauchi T, Itoh S, Kumagai H et al (2007) Adiponectin stimulates AMP-activated protein kinase in the hypothalamus and increases food intake. Cell Metab 6(1):55–68

    Article  CAS  PubMed  Google Scholar 

  65. Szrejder M, Piwkowska A (2019) AMPK signalling: implications for podocyte biology in diabetic nephropathy. Biol Cell 111(5):109–120. https://doi.org/10.1111/boc.201800077

    Article  PubMed  Google Scholar 

  66. Hardie DG, Scott JW, Pan DA, Hudson ER (2003) Management of cellular energy by the AMP-activated protein kinase system. FEBS Lett 546(1):113–120

    Article  CAS  PubMed  Google Scholar 

  67. Kurumbail RG, Calabrese MF (2012) Structure and regulation of AMPK. Exp Suppl 2016:107

    Google Scholar 

  68. Szymańska P, Martin KR, MacKeigan JP, Hlavacek WS, Lipniacki T (2015) Computational analysis of an autophagy/translation switch based on mutual inhibition of MTORC1 and ULK1. PLoS ONE 10(3):e0116550. https://doi.org/10.1371/journal.pone.0116550

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Willows R, Sanders MJ, Xiao B, Patel BR, Martin SR, Read J et al (2017) Phosphorylation of AMPK by upstream kinases is required for activity in mammalian cells. Biochem J 474(17):3059–3073. https://doi.org/10.1042/bcj20170458

    Article  CAS  PubMed  Google Scholar 

  70. Nishi H, Higashihara T, Inagi R (2019) Lipotoxicity in kidney, heart, and skeletal muscle dysfunction. Nutrients. https://doi.org/10.3390/nu11071664

    Article  PubMed  PubMed Central  Google Scholar 

  71. Kim Y, Park CW (2016) Adenosine monophosphate-activated protein kinase in diabetic nephropathy. Kidney Res Clin Pract 35(2):69–77. https://doi.org/10.1016/j.krcp.2016.02.004

    Article  PubMed  PubMed Central  Google Scholar 

  72. Kim Y, Lim JH, Kim MY, Kim EN, Yoon HE, Shin SJ et al (2018) The adiponectin receptor agonist AdipoRon ameliorates diabetic nephropathy in a model of type 2 diabetes. J Am Soc Nephrol JASN 29(4):1108–1127. https://doi.org/10.1681/asn.2017060627

    Article  CAS  PubMed  Google Scholar 

  73. Sanders MJ, Ali ZS, Hegarty BD, Heath R, Snowden MA, Carling D (2007) Defining the mechanism of activation of AMP-activated protein kinase by the small molecule A-769662, a member of the thienopyridone family. J Biol Chem 282(45):32539–32548

    Article  CAS  PubMed  Google Scholar 

  74. Nusse R, Clevers H (2017) Wnt/β-catenin signaling, disease, and emerging therapeutic modalities. Cell 169(6):985–999

    Article  CAS  PubMed  Google Scholar 

  75. Zhou D, Tan RJ, Fu H, Liu Y (2016) Wnt/β-catenin signaling in kidney injury and repair: a double-edged sword. Lab Invest 96(2):156–167. https://doi.org/10.1038/labinvest.2015.153

    Article  CAS  PubMed  Google Scholar 

  76. Luo C, Zhou S, Zhou Z, Liu Y, Yang L, Liu J et al (2018) Wnt9a promotes renal fibrosis by accelerating cellular senescence in tubular epithelial cells. J Am Soc Nephrol JASN 29(4):1238–1256. https://doi.org/10.1681/ASN.2017050574

    Article  CAS  PubMed  Google Scholar 

  77. Wang Y, Zhou CJ, Liu Y (2018) Wnt Signaling in kidney development and disease. Prog Mol Biol Transl Sci 153:181–207

    Article  CAS  PubMed  Google Scholar 

  78. Feng Y, Ren J, Gui Y, Wei W, Shu B, Lu Q et al (2018) Wnt/-catenin-promoted macrophage alternative activation contributes to kidney fibrosis. J Am Soc Nephrol JASN 29(1):182–193. https://doi.org/10.1681/ASN.2017040391

    Article  CAS  PubMed  Google Scholar 

  79. Miao J, Liu J, Niu J, Zhang Y, Shen W, Luo C et al (2019) Wnt/beta-catenin/RAS signaling mediates age-related renal fibrosis and is associated with mitochondrial dysfunction. Aging Cell 18(5):e13004. https://doi.org/10.1111/acel.13004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Liu B-L, Chen Y-P, Cheng H, Wang Y-Y, Rui H-L, Yang M et al (2015) The protective effects of curcumin on obesity-related glomerulopathy are associated with inhibition of Wnt/β-catenin signaling activation in podocytes. Evid Based Complement Altern Med 2015:827472. https://doi.org/10.1155/2015/827472

    Article  Google Scholar 

  81. Kato H, Gruenwald A, Suh JH, Miner JH, Barisoni-Thomas L, Taketo MM et al (2011) Wnt/β-catenin pathway in podocytes integrates cell adhesion, differentiation, and survival. J Biol Chem 286(29):26003–26015. https://doi.org/10.1074/jbc.M111.223164

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Zhang H, Mao X, Sun Y, Hu R, Luo W, Zhao Z et al (2015) NF-κB upregulates ubiquitin C-terminal hydrolase 1 in diseased podocytes in glomerulonephritis. Mol Med Rep 12(2):2893–2901. https://doi.org/10.3892/mmr.2015.3780

    Article  CAS  PubMed  Google Scholar 

  83. Zhang H, Luo W, Sun Y, Qiao Y, Zhang L, Zhao Z et al (2016) Wnt/β-catenin signaling mediated-UCH-L1 expression in podocytes of diabetic nephropathy. Int J Mol Sci. https://doi.org/10.3390/ijms17091404

    Article  PubMed  PubMed Central  Google Scholar 

  84. Yoon JC, Ng A, Kim BH, Bianco A, Xavier RJ, Elledge SJ (2010) Wnt signaling regulates mitochondrial physiology and insulin sensitivity. Genes Dev 24(14):1507–1518. https://doi.org/10.1101/gad.1924910

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Li Z, Xu J, Xu P, Liu S, Yang Z (2013) Wnt/β-catenin signalling pathway mediates high glucose induced cell injury through activation of TRPC6 in podocytes. Cell Prolif 46(1):76–85. https://doi.org/10.1111/cpr.12010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Saxton RA, Sabatini DM (2017) mTOR Signaling in growth, metabolism, and disease. Cell 169(2):361–371

    Article  CAS  PubMed  Google Scholar 

  87. Kajiwara M, Masuda S (2016) Role of mTOR inhibitors in kidney disease. Int J Mol Sci. https://doi.org/10.3390/ijms17060975

    Article  PubMed  PubMed Central  Google Scholar 

  88. Yao Y, Wang J, Yoshida S, Nada S, Okada M, Inoki K (2016) Role of regulator in the regulation of mechanistic target of rapamycin signaling in podocytes and glomerular function. J Am Soc Nephrol JASN 27(12):3653–3665

    Article  CAS  PubMed  Google Scholar 

  89. Skała E, Sitarek P, Toma M, Szemraj J, Radek M, Nieborowska-Skorska M et al (2016) Inhibition of human glioma cell proliferation by altered Bax/Bcl-2-p53 expression and apoptosis induction by Rhaponticum carthamoides extracts from transformed and normal roots. J Pharm Pharmacol 68(11):1454–1464. https://doi.org/10.1111/jphp.12619

    Article  CAS  PubMed  Google Scholar 

  90. Shi H, Zhang A, He Y, Yang M, Gan W (2016) Effects of p53 on aldosterone-induced mesangial cell apoptosis in vivo and in vitro. Mol Med Rep 13(6):5102–5108. https://doi.org/10.3892/mmr.2016.5156

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Morita M, Gravel S-P, Chénard V, Sikström K, Zheng L, Alain T et al (2013) mTORC1 controls mitochondrial activity and biogenesis through 4E-BP-dependent translational regulation. Cell Metab 18(5):698–711. https://doi.org/10.1016/j.cmet.2013.10.001

    Article  CAS  PubMed  Google Scholar 

  92. Fantus D, Rogers NM, Grahammer F, Huber TB, Thomson AW (2016) Roles of mTOR complexes in the kidney: implications for renal disease and transplantation. Nat Rev Nephrol 12(10):587–609. https://doi.org/10.1038/nrneph.2016.108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Morita M, Gravel SP, Hulea L, Larsson O, Pollak M, St-Pierre J et al (2015) mTOR coordinates protein synthesis, mitochondrial activity and proliferation. Cell Cycle 14(4):473–480. https://doi.org/10.4161/15384101.2014.991572

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Gao P, Li L, Yang L, Gui D, Zhang J, Han J et al (2019) Yin Yang 1 protein ameliorates diabetic nephropathy pathology through transcriptional repression of TGFβ1. Sci Transl Med. https://doi.org/10.1126/scitranslmed.aaw2050

    Article  PubMed  PubMed Central  Google Scholar 

  95. Yao Y, Inoki K (2016) The role of mechanistic target of rapamycin in maintenance of glomerular epithelial cells. Curr Opin Nephrol Hypertens 25(1):28–34. https://doi.org/10.1097/MNH.0000000000000181

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Inoki K, Mori H, Wang J, Suzuki T, Hong S, Yoshida S et al (2011) mTORC1 activation in podocytes is a critical step in the development of diabetic nephropathy in mice. J Clin Investig 121(6):2181–2196. https://doi.org/10.1172/JCI44771

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Gödel M, Hartleben B, Herbach N, Liu S, Zschiedrich S, Lu S et al (2011) Role of mTOR in podocyte function and diabetic nephropathy in humans and mice. J Clin Investig 121(6):2197–2209. https://doi.org/10.1172/JCI44774

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Canaud G, Bienaimé F, Viau A, Treins C, Baron W, Nguyen C et al (2013) AKT2 is essential to maintain podocyte viability and function during chronic kidney disease. Nat Med 19(10):1288–1296. https://doi.org/10.1038/nm.3313

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This paper did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations

  1. Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, 200233, China

    Jun Su, Chongting Gao, Qunwei Huang & Dingkun Gui

  2. Shanghai Ocean University, Shanghai, 201306, China

    Dan Ye

Authors
  1. Jun Su
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dan Ye
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chongting Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Qunwei Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dingkun Gui
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dingkun Gui.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Human and animal rights

This article does not contain any studies with human or animal subjects performed by any of the authors.

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

Su, J., Ye, D., Gao, C. et al. Mechanism of progression of diabetic kidney disease mediated by podocyte mitochondrial injury. Mol Biol Rep 47, 8023–8035 (2020). https://doi.org/10.1007/s11033-020-05749-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-020-05749-0

Keywords

Search

Navigation