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PGC1-α in diabetic kidney disease: unraveling renoprotection and molecular mechanisms

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Abstract

Mitochondrial dysfunction represents a pivotal aspect of the pathogenesis and progression of diabetic kidney disease (DKD). Central to the orchestration of mitochondrial biogenesis is the peroxisome proliferator-activated receptor γ coactivator 1-α (PGC1-α), a master regulator with a profound impact on mitochondrial function. In the context of DKD, PGC1-α exhibits significant downregulation within intrinsic renal cells, precipitating a cascade of deleterious events. This includes a reduction in mitochondrial biogenesis, heightened levels of mitochondrial oxidative stress, perturbed mitochondrial dynamics, and dysregulated mitophagy. Concurrently, structural and functional abnormalities within the mitochondrial network ensue. In stark contrast, the sustained expression of PGC1-α emerges as a beacon of hope in maintaining mitochondrial homeostasis within intrinsic renal cells, ultimately demonstrating an impressive renoprotective potential in animal models afflicted with DKD. This comprehensive review aims to delve into the recent advancements in our understanding of the renoprotective properties wielded by PGC1-α. Specifically, it elucidates the potential molecular mechanisms underlying PGC1-α’s protective effects within renal tubular epithelial cells, podocytes, glomerular endothelial cells, and mesangial cells in the context of DKD. By shedding light on these intricate mechanisms, we aspire to provide valuable insights that may pave the way for innovative therapeutic interventions in the management of DKD.

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All data generated or analyzed during this study are included in this published article.

Abbreviations

DKD:

Diabetic kidney disease

ATP:

Adenosine triphosphate

ROS:

Reactive oxygen species

PGC1-α:

Peroxisome proliferator-activated receptor γ coactivator 1-α

PPARGC1A:

Peroxisome proliferator-activated receptor gamma coactivator 1 alpha

NRF:

Nuclear respiratory factor

MC:

Mitochondrial respiratory chain complex

ERR:

Estrogen-related receptor

MFN1:

Mitofusin-1

TFAM:

Mitochondrial transcriptional factor A

mtDNA:

Mitochondrial DNA

STZ:

Streptozotocin

SOD:

Superoxide dismutase

DRP1:

Dynamic-related protein 1

BAX:

BCL2-associated X

TLR4:

Toll-like receptor 4

LXRs/ABCA1:

Liver X receptors/ATP-binding cassette subfamily A member 1

NEFA:

Non-esterified fatty acid

SIRT:

Sirtuin

8-OHdG:

8-Hydroxydeoxyguanosine

PGRN:

Progranulin

hEC-SOD:

Human extracellular superoxide dismutase

PRR:

(Pro)renin receptor

CHOP:

C/EBP homologous protein

GCS:

γ-Glutamylcysteine synthase

NQO1:

NAD(P)H dehydrogenase quinone 1

HO1:

Heme oxygenase-1

GSH:

Glutathione

GSH-Px:

Glutathione peroxidase

NOX:

NADPH oxidase

CPT1:

Carnitine palmitoyltransferase 1

MCAD:

Medium-chain acyl-CoA dehydrogenase

PDK4:

Pyruvate dehydrogenase kinase 4

TRG:

Triglyceride

CHOL:

Cholesterol

OPA1:

Optic atrophy 1

TUG1:

Taurine-upregulated gene 1

DPP-4:

Dipeptidyl peptidase-4

KEAP1:

Kelch-like epichlorohydrin-associated protein 1

GLP-1:

Glucagon-like peptide-1

Ang II:

Angiotensin II

References

  1. Zhang L, Long J, Jiang W, Shi Y, He X, Zhou Z, Li Y, Yeung RO, Wang J, Matsushita K et al (2016) Trends in chronic kidney disease in China. N Engl J Med 375:905–906

    Article  PubMed  Google Scholar 

  2. Wang F, Yang C, Long J, Zhao X, Tang W, Zhang D, Bai K, Su Z, Gao B, Chu H et al (2019) Executive summary for the 2015 annual data report of the china kidney disease network (CK-NET). Kidney Int 95:501–505

    Article  PubMed  Google Scholar 

  3. Zhang L, Zuo L (2016) Current burden of end-stage kidney disease and its future trend in China. Clin Nephrol 2016(86):27–28

    Article  Google Scholar 

  4. Tang SCW, Yiu WH (2020) Innate immunity in diabetic kidney disease. Nat Rev Nephrol 16:206–222

    Article  CAS  PubMed  Google Scholar 

  5. Mima A (2022) A narrative review of diabetic kidney disease: previous and current evidence-based therapeutic approaches. Adv Ther 39:3488–3500

    Article  PubMed  Google Scholar 

  6. Mima A (2013) Inflammation and oxidative stress in diabetic nephropathy: new insights on its inhibition as new therapeutic targets. J Diabetes Res 2013:248563

    Article  PubMed  PubMed Central  Google Scholar 

  7. Liu Y, Uruno A, Saito R, Matsukawa N, Hishinuma E, Saigusa D, Liu H, Yamamoto M (2022) Nrf2 deficiency deteriorates diabetic kidney disease in Akita model mice. Redox Biol 58:102525

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Wu CC, Chen JS, Lu KC, Chen CC, Lin SH, Chu P, Sytwu HK, Lin YF (2010) Aberrant cytokines/chemokines production correlate with proteinuria in patients with overt diabetic nephropathy. Clin Chim Acta 411:700–704

    Article  CAS  PubMed  Google Scholar 

  9. Mitrofanova A, Fontanella A, Tolerico M, Mallela S, Molina David J, Zuo Y, Boulina M, Kim JJ, Santos J, Ge M et al (2022) Activation of stimulator of IFN genes (STING) causes proteinuria and contributes to glomerular diseases. J Am Soc Nephrol 33:2153–2173

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Foresto-Neto O, Albino AH, Arias SCA, Faustino VD, Zambom FFF, Cenedeze MA, Elias RM, Malheiros D, Camara NOS, Fujihara CK, Zatz R (2020) NF-kappaB system is chronically activated and promotes glomerular injury in experimental type 1 diabetic kidney disease. Front Physiol 11:84

    Article  PubMed  PubMed Central  Google Scholar 

  11. Mitrofanova A, Fontanella AM, Burke GW, Merscher S, Fornoni A (2022) Mitochondrial contribution to inflammation in diabetic kidney disease. Cells 11:3635

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Ahmad AA, Draves SO, Rosca M (2021) Mitochondria in diabetic kidney disease. Cells 10:2945

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Mima A, Qi W, King GL (2012) Implications of treatment that target protective mechanisms against diabetic nephropathy. Semin Nephrol 32:471–478

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Galvan DL, Green NH, Danesh FR (2017) The hallmarks of mitochondrial dysfunction in chronic kidney disease. Kidney Int 92:1051–1057

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Fontecha-Barriuso M, Martin-Sanchez D, Martinez-Moreno JM, Monsalve M, Ramos AM, Sanchez-Nino MD, Ruiz-Ortega M, Ortiz A, Sanz AB (2020) The Role of PGC-1alpha and mitochondrial biogenesis in kidney diseases. Biomolecules 10:347

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Audzeyenka I, Rachubik P, Typiak M, Kulesza T, Topolewska A, Rogacka D, Angielski S, Saleem MA, Piwkowska A (2021) Hyperglycemia alters mitochondrial respiration efficiency and mitophagy in human podocytes. Exp Cell Res 407:112758

    Article  CAS  PubMed  Google Scholar 

  17. Jiang XS, Chen XM, Hua W, He JL, Liu T, Li XJ, Wan JM, Gan H, Du XG (2020) PINK1/Parkin mediated mitophagy ameliorates palmitic acid-induced apoptosis through reducing mitochondrial ROS production in podocytes. Biochem Biophys Res Commun 525:954–961

    Article  CAS  PubMed  Google Scholar 

  18. Yu T, Sheu SS, Robotham JL, Yoon Y (2008) Mitochondrial fission mediates high glucose-induced cell death through elevated production of reactive oxygen species. Cardiovasc Res 79:341–351

    Article  CAS  PubMed  Google Scholar 

  19. Li B, Leung JCK, Chan LYY, Li HY, Yiu WH, Lok SWY, Xue R, Zou YX, Chen W, Lai KN, Tang SCW (2021) Tubule-specific deletion of LincRNA-p21ameliorates lipotoxic kidney injury. Mol Ther Nucleic Acids 26:1280–1290

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Li B, Leung JCK, Chan LYY, Yiu WH, Li Y, Lok SWY, Liu WH, Chan KW, Tse HF, Lai KN, Tang SCW (2019) Amelioration of endoplasmic reticulum stress by mesenchymal stem cells via hepatocyte growth factor/c-met signaling in obesity-associated kidney injury. Stem Cells Transl Med 8:898–910

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Sidarala V, Pearson GL, Parekh VS, Thompson B, Christen L, Gingerich MA, Zhu J, Stromer T, Ren J, Reck EC et al (2020) Mitophagy protects beta cells from inflammatory damage in diabetes. JCI Insight. https://doi.org/10.1172/jci.insight.141138

    Article  PubMed  PubMed Central  Google Scholar 

  22. Sha W, Hu F, Bu S (2020) Mitochondrial dysfunction and pancreatic islet beta-cell failure (Review). Exp Ther Med 20:266

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Mima A (2022) Mitochondria-targeted drugs for diabetic kidney disease. Heliyon 8:e08878

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Rana R, Manoharan J, Gupta A, Gupta D, Elwakiel A, Khawaja H, Fatima S, Zimmermann S, Singh K, Ambreen S et al (2022) Activated protein C ameliorates tubular mitochondrial reactive oxygen species and inflammation in diabetic kidney disease. Nutrients 14:3188

    Article  Google Scholar 

  25. Liu WJ, Reiser J, Park TS, Liu Z, Ishibe S (2017) New insights into diabetic kidney disease: the potential pathogenesis and therapeutic targets. J Diabetes Res 2017:3945469

    Article  PubMed  PubMed Central  Google Scholar 

  26. Guo K, Lu J, Huang Y, Wu M, Zhang L, Yu H, Zhang M, Bao Y, He JC, Chen H, Jia W (2015) Protective role of PGC-1alpha in diabetic nephropathy is associated with the inhibition of ROS through mitochondrial dynamic remodeling. PLoS ONE 10:e0125176

    Article  PubMed  PubMed Central  Google Scholar 

  27. Sharma K, Karl B, Mathew AV, Gangoiti JA, Wassel CL, Saito R, Pu M, Sharma S, You YH, Wang L et al (2013) Metabolomics reveals signature of mitochondrial dysfunction in diabetic kidney disease. J Am Soc Nephrol 24:1901–1912

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Imasawa T, Obre E, Bellance N, Lavie J, Imasawa T, Rigothier C, Delmas Y, Combe C, Lacombe D, Benard G et al (2017) High glucose repatterns human podocyte energy metabolism during differentiation and diabetic nephropathy. FASEB J 31:294–307

    Article  CAS  PubMed  Google Scholar 

  29. Li L, Wang CS, Yang HL, Liu SY, Lu YR, Fu P, Liu JP (2017) Metabolomics reveal mitochondrial and fatty acid metabolism disorders that contribute to the development of DKD in T2DM patients. Mol BioSyst 13:2392–2400

    Article  CAS  PubMed  Google Scholar 

  30. Martinez-Redondo V, Pettersson AT, Ruas JL (2015) The hitchhiker’s guide to PGC-1alpha isoform structure and biological functions. Diabetologia 58:1969–1977

    Article  CAS  PubMed  Google Scholar 

  31. Luo C, Widlund HR, Puigserver P (2016) PGC-1 coactivators: shepherding the mitochondrial biogenesis of tumors. Trends Cancer 2:619–631

    Article  PubMed  PubMed Central  Google Scholar 

  32. Lin J, Handschin C, Spiegelman BM (2005) Metabolic control through the PGC-1 family of transcription coactivators. Cell Metab 1:361–370

    Article  PubMed  Google Scholar 

  33. Handschin C, Spiegelman BM (2006) Peroxisome proliferator-activated receptor gamma coactivator 1 coactivators, energy homeostasis, and metabolism. Endocr Rev 27:728–735

    Article  CAS  PubMed  Google Scholar 

  34. Fernandez-Marcos PJ, Auwerx J (2011) Regulation of PGC-1alpha, a nodal regulator of mitochondrial biogenesis. Am J Clin Nutr 93:884S – 890

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Patten IS, Arany Z (2012) PGC-1 coactivators in the cardiovascular system. Trends Endocrinol Metab 23:90–97

    Article  CAS  PubMed  Google Scholar 

  36. Li SY, Susztak K (2018) The role of peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) in kidney disease. Semin Nephrol 38:121–126

    Article  PubMed  PubMed Central  Google Scholar 

  37. Bhatti JS, Bhatti GK, Reddy PH (2017) Mitochondrial dysfunction and oxidative stress in metabolic disorders—a step towards mitochondria based therapeutic strategies. Biochim Biophys Acta Mol Basis Dis 1863:1066–1077

    Article  CAS  PubMed  Google Scholar 

  38. Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G, Mootha V, Troy A, Cinti S, Lowell B, Scarpulla RC, Spiegelman BM (1999) Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 98:115–124

    Article  CAS  PubMed  Google Scholar 

  39. Aggarwal R, Potel KN, McFalls EO, Butterick TA, Kelly RF (2022) Novel therapeutic approaches enhance PGC1-alpha to reduce oxidant stress-inflammatory signaling and improve functional recovery in hibernating myocardium. Antioxidants (Basel) 11:2155

    Article  PubMed  PubMed Central  Google Scholar 

  40. Yuan Y, Yuan L, Li L, Liu F, Liu J, Chen Y, Cheng J, Lu Y (2021) Mitochondrial transfer from mesenchymal stem cells to macrophages restricts inflammation and alleviates kidney injury in diabetic nephropathy mice via PGC-1alpha activation. Stem Cells 39:913–928

    Article  CAS  PubMed  Google Scholar 

  41. Jeong HY, Kang JM, Jun HH, Kim DJ, Park SH, Sung MJ, Heo JH, Yang DH, Lee SH, Lee SY (2018) Chloroquine and amodiaquine enhance AMPK phosphorylation and improve mitochondrial fragmentation in diabetic tubulopathy. Sci Rep 8:8774

    Article  PubMed  PubMed Central  ADS  Google Scholar 

  42. Lakshmanan AP, Watanabe K, Thandavarayan RA, Sari FR, Harima M, Giridharan VV, Soetikno V, Kodama M, Aizawa Y (2011) Telmisartan attenuates oxidative stress and renal fibrosis in streptozotocin induced diabetic mice with the alteration of angiotensin-(1–7) mas receptor expression associated with its PPAR-gamma agonist action. Free Radic Res 45:575–584

    Article  CAS  PubMed  Google Scholar 

  43. Qin X, Jiang M, Zhao Y, Gong J, Su H, Yuan F, Fang K, Yuan X, Yu X, Dong H, Lu F (2020) Berberine protects against diabetic kidney disease via promoting PGC-1alpha-regulated mitochondrial energy homeostasis. Br J Pharmacol 177:3646–3661

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Locatelli M, Zoja C, Zanchi C, Corna D, Villa S, Bolognini S, Novelli R, Perico L, Remuzzi G, Benigni A, Cassis P (2020) Manipulating Sirtuin 3 pathway ameliorates renal damage in experimental diabetes. Sci Rep 10:8418

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  45. Zhang T, Chi Y, Kang Y, Lu H, Niu H, Liu W, Li Y (2018) Resveratrol ameliorates podocyte damage in diabetic mice via SIRT1/PGC-1α mediated attenuation of mitochondrial oxidative stress. J Cell Physiol 234:5033–5043

    Article  PubMed  Google Scholar 

  46. Xue H, Li P, Luo Y, Wu C, Liu Y, Qin X, Huang X, Sun C (2019) Salidroside stimulates the Sirt1/PGC-1alpha axis and ameliorates diabetic nephropathy in mice. Phytomedicine 54:240–247

    Article  CAS  PubMed  Google Scholar 

  47. Shen H, Ming Y, Xu C, Xu Y, Zhao S, Zhang Q (2019) Deregulation of long noncoding RNA (TUG1) contributes to excessive podocytes apoptosis by activating endoplasmic reticulum stress in the development of diabetic nephropathy. J Cell Physiol 234:15123–15133

    Article  CAS  PubMed  Google Scholar 

  48. Ma T, Zheng Z, Guo H, Lian X, Rane MJ, Cai L, Kim KS, Kim KT, Zhang Z, Bi L (2019) 4-O-methylhonokiol ameliorates type 2 diabetes-induced nephropathy in mice likely by activation of AMPK-mediated fatty acid oxidation and Nrf2-mediated anti-oxidative stress. Toxicol Appl Pharmacol 370:93–105

    Article  CAS  PubMed  Google Scholar 

  49. Liao Z, Zhang J, Wang J, Yan T, Xu F, Wu B, Xiao F, Bi K, Niu J, Jia Y (2019) The anti-nephritic activity of a polysaccharide from okra (Abelmoschus esculentus (L.) Moench) via modulation of AMPK-Sirt1-PGC-1alpha signaling axis mediated anti-oxidative in type 2 diabetes model mice. Int J Biol Macromol 140:568–576

    Article  CAS  PubMed  Google Scholar 

  50. Akhtar S, Siragy HM (2019) Pro-renin receptor suppresses mitochondrial biogenesis and function via AMPK/SIRT-1/ PGC-1alpha pathway in diabetic kidney. PLoS ONE 14:e0225728

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Yuan S, Liu X, Zhu X, Qu Z, Gong Z, Li J, Xiao L, Yang Y, Liu H, Sun L, Liu F (2018) The role of TLR4 on PGC-1alpha-mediated oxidative stress in tubular cell in diabetic kidney disease. Oxid Med Cell Longev 2018:6296802

    Article  PubMed  PubMed Central  Google Scholar 

  52. Wang XX, Wang D, Luo Y, Myakala K, Dobrinskikh E, Rosenberg AZ, Levi J, Kopp JB, Field A, Hill A et al (2018) FXR/TGR5 dual agonist prevents progression of nephropathy in diabetes and obesity. J Am Soc Nephrol 29:118–137

    Article  CAS  PubMed  Google Scholar 

  53. Sun W, Wang Y, Miao X, Wang Y, Zhang L, Xin Y, Zheng S, Epstein PN, Fu Y, Cai L (2014) Renal improvement by zinc in diabetic mice is associated with glucose metabolism signaling mediated by metallothionein and Akt, but not Akt2. Free Radic Biol Med 68:22–34

    Article  CAS  PubMed  Google Scholar 

  54. Zhang L, Liu J, Zhou F, Wang W, Chen N (2018) PGC-1alpha ameliorates kidney fibrosis in mice with diabetic kidney disease through an antioxidative mechanism. Mol Med Rep 17:4490–4498

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Hong YA, Lim JH, Kim MY, Kim Y, Park HS, Kim HW, Choi BS, Chang YS, Kim HW, Kim TY, Park CW (2018) Extracellular superoxide dismutase attenuates renal oxidative stress through the activation of adenosine monophosphate-activated protein kinase in diabetic nephropathy. Antioxid Redox Signal 28:1543–1561

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Zhou D, Zhou M, Wang Z, Fu Y, Jia M, Wang X, Liu M, Zhang Y, Sun Y, Lu Y et al (2019) PGRN acts as a novel regulator of mitochondrial homeostasis by facilitating mitophagy and mitochondrial biogenesis to prevent podocyte injury in diabetic nephropathy. Cell Death Dis 10:524

    Article  PubMed  PubMed Central  Google Scholar 

  57. Li SY, Park J, Qiu C, Han SH, Palmer MB, Arany Z, Susztak K (2017) Increasing the level of peroxisome proliferator-activated receptor gamma coactivator-1alpha in podocytes results in collapsing glomerulopathy. JCI Insight. https://doi.org/10.1172/jci.insight.92930

    Article  PubMed  PubMed Central  Google Scholar 

  58. Long J, Badal SS, Ye Z, Wang Y, Ayanga BA, Galvan DL, Green NH, Chang BH, Overbeek PA, Danesh FR (2016) Long noncoding RNA Tug1 regulates mitochondrial bioenergetics in diabetic nephropathy. J Clin Invest 126:4205–4218

    Article  PubMed  PubMed Central  Google Scholar 

  59. Kim MY, Lim JH, Youn HH, Hong YA, Yang KS, Park HS, Chung S, Ko SH, Shin SJ, Choi BS et al (2013) Resveratrol prevents renal lipotoxicity and inhibits mesangial cell glucotoxicity in a manner dependent on the AMPK-SIRT1-PGC1alpha axis in db/db mice. Diabetologia 56:204–217

    Article  CAS  PubMed  Google Scholar 

  60. Wang X, Meng L, Zhao L, Wang Z, Liu H, Liu G, Guan G (2017) Resveratrol ameliorates hyperglycemia-induced renal tubular oxidative stress damage via modulating the SIRT1/FOXO3a pathway. Diabetes Res Clin Pract 126:172–181

    Article  CAS  PubMed  Google Scholar 

  61. Wang Y, Wang B, Qi X, Zhang X, Ren K (2019) Resveratrol protects against post-contrast acute kidney injury in rabbits with diabetic nephropathy. Front Pharmacol 10:833

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Cleveland KH, Schnellmann RG (2023) Pharmacological targeting of mitochondria in diabetic kidney disease. Pharmacol Rev 75:250–262

    Article  CAS  PubMed  Google Scholar 

  63. Liu P, Peng L, Zhang H, Tang PM, Zhao T, Yan M, Zhao H, Huang X, Lan H, Li P (2018) Tangshen formula attenuates diabetic nephropathy by promoting ABCA1-mediated renal cholesterol efflux in db/db mice. Front Physiol 9:343

    Article  PubMed  PubMed Central  Google Scholar 

  64. Xiao L, Zhu X, Yang S, Liu F, Zhou Z, Zhan M, Xie P, Zhang D, Li J, Song P et al (2014) Rap1 ameliorates renal tubular injury in diabetic nephropathy. Diabetes 63:1366–1380

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Dorotea D, Cho A, Lee G, Kwon G, Lee J, Sahu PK, Jeong LS, Cha DR, Ha H (2018) Orally active, species-independent novel A(3) adenosine receptor antagonist protects against kidney injury in db/db mice. Exp Mol Med 50:1–14

    Article  CAS  PubMed  Google Scholar 

  66. Deng QX, Wen RW, Liu SR, Chen XQ, Song SC, Li XH, Su ZZ, Wang C (2020) Increased long noncoding RNA maternally expressed gene 3 contributes to podocyte injury induced by high glucose through regulation of mitochondrial fission. Cell Death Dis. https://doi.org/10.1038/s41419-020-03022-7

    Article  PubMed  PubMed Central  Google Scholar 

  67. Qi W, Keenan HA, Li Q, Ishikado A, Kannt A, Sadowski T, Yorek MA, Wu IH, Lockhart S, Coppey LJ et al (2017) Pyruvate kinase M2 activation may protect against the progression of diabetic glomerular pathology and mitochondrial dysfunction. Nat Med 23:753–762

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Han S-H (2009) Potential role of sirtuin as a therapeutic target for neurodegenerative diseases. J Clin Neurol 5:120–125

    Article  PubMed  PubMed Central  Google Scholar 

  69. Hong Q, Zhang L, Das B, Li Z, Liu B, Cai G, Chen X, Chuang PY, He JC, Lee K (2018) Increased podocyte Sirtuin-1 function attenuates diabetic kidney injury. Kidney Int 93:1330–1343

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Park HS, Lim JH, Kim MY, Kim Y, Hong YA, Choi SR, Chung S, Kim HW, Choi BS, Kim YS et al (2016) Resveratrol increases AdipoR1 and AdipoR2 expression in type 2 diabetic nephropathy. J Transl Med 14:176

    Article  PubMed  PubMed Central  Google Scholar 

  71. 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 39:341–349

    Article  CAS  PubMed  Google Scholar 

  72. Mima A, Yasuzawa T, Nakamura T, Ueshima S (2020) Linagliptin affects IRS1/Akt signaling and prevents high glucose-induced apoptosis in podocytes. Sci Rep 10:5775

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  73. Takashima S, Fujita H, Fujishima H, Shimizu T, Sato T, Morii T, Tsukiyama K, Narita T, Takahashi T, Drucker DJ et al (2016) Stromal cell-derived factor-1 is upregulated by dipeptidyl peptidase-4 inhibition and has protective roles in progressive diabetic nephropathy. Kidney Int 90:783–796

    Article  CAS  PubMed  Google Scholar 

  74. Kubo A, Hidaka T, Nakayama M, Sasaki Y, Takagi M, Suzuki H, Suzuki Y (2020) Protective effects of DPP-4 inhibitor on podocyte injury in glomerular diseases. BMC Nephrol 21:402

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Cherry AD, Suliman HB, Bartz RR, Piantadosi CA (2014) Peroxisome proliferator-activated receptor gamma co-activator 1-alpha as a critical co-activator of the murine hepatic oxidative stress response and mitochondrial biogenesis in Staphylococcus aureus sepsis. J Biol Chem 289:41–52

    Article  CAS  PubMed  Google Scholar 

  76. Mima A, Hiraoka-Yamomoto J, Li Q, Kitada M, Li C, Geraldes P, Matsumoto M, Mizutani K, Park K, Cahill C et al (2012) Protective effects of GLP-1 on glomerular endothelium and its inhibition by PKCbeta activation in diabetes. Diabetes 61:2967–2979

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Yin W, Jiang Y, Xu S, Wang Z, Peng L, Fang Q, Deng T, Zhao W, Zhang W, Lou J (2019) Protein kinase C and protein kinase A are involved in the protection of recombinant human glucagon-like peptide-1 on glomeruli and tubules in diabetic rats. J Diabetes Investig 10:613–625

    Article  CAS  PubMed  Google Scholar 

  78. Einbinder Y, Ohana M, Benchetrit S, Zehavi T, Nacasch N, Bernheim J, Zitman-Gal T (2016) Glucagon-like peptide-1 and vitamin D: anti-inflammatory response in diabetic kidney disease in db/db mice and in cultured endothelial cells. Diabetes Metab Res Rev 32:805–815

    Article  CAS  PubMed  Google Scholar 

  79. Mima A, Ohshiro Y, Kitada M, Matsumoto M, Geraldes P, Li C, Li Q, White GS, Cahill C, Rask-Madsen C, King GL (2011) Glomerular-specific protein kinase C-beta-induced insulin receptor substrate-1 dysfunction and insulin resistance in rat models of diabetes and obesity. Kidney Int 79:883–896

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Taguchi S, Azushima K, Yamaji T, Suzuki T, Abe E, Tanaka S, Hirota K, Tsukamoto S, Morita R, Kobayashi R et al (2023) Angiotensin II type 1 receptor-associated protein deletion combined with angiotensin II stimulation accelerates the development of diabetic kidney disease in mice on a C57BL/6 strain. Hypertens Res 47:55

    Article  PubMed  Google Scholar 

  81. Xiong S, Salazar G, San Martin A, Ahmad M, Patrushev N, Hilenski L, Nazarewicz RR, Ma M, Ushio-Fukai M, Alexander RW (2010) PGC-1 alpha serine 570 phosphorylation and GCN5-mediated acetylation by angiotensin II drive catalase down-regulation and vascular hypertrophy. J Biol Chem 285:2474–2487

    Article  CAS  PubMed  Google Scholar 

  82. Al-Kafaji G, Sabry MA, Skrypnyk C (2016) Time-course effect of high-glucose-induced reactive oxygen species on mitochondrial biogenesis and function in human renal mesangial cells. Cell Biol Int 40:36–48

    Article  CAS  PubMed  Google Scholar 

  83. Hong YA, Lim JH, Kim MY, Kim TW, Kim Y, Yang KS, Park HS, Choi SR, Chung S, Kim HW et al (2014) Fenofibrate improves renal lipotoxicity through activation of AMPK-PGC-1alpha in db/db mice. PLoS ONE 9:e96147

    Article  PubMed  PubMed Central  ADS  Google Scholar 

  84. Bao L, Cai X, Zhang Z, Li Y (2015) Grape seed procyanidin B2 ameliorates mitochondrial dysfunction and inhibits apoptosis via the AMP-activated protein kinase-silent mating type information regulation 2 homologue 1-PPARgamma co-activator-1alpha axis in rat mesangial cells under high-dose glucosamine. Br J Nutr 113:35–44

    Article  CAS  PubMed  Google Scholar 

  85. Cai X, Bao L, Ren J, Li Y, Zhang Z (2016) Grape seed procyanidin B2 protects podocytes from high glucose-induced mitochondrial dysfunction and apoptosis via the AMPK-SIRT1-PGC-1alpha axis in vitro. Food Funct 7:805–815

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We gratefully acknowledge Ruobing Wang for providing intellectual support and helpful discussions.

Funding

This research was supported by grants from the National Natural Science Foundation of China (No. 82100747, No. 82170737, No. 81970599, No. 82370707); the Guangdong Provincial Key Laboratory of Nephrology (No. 2020B1212060028); the NHC Key Laboratory of Clinical Nephrology (Sun Yat-sen University).

Author information

Authors and Affiliations

  1. Department of Nephrology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China

    Siyang Ye, Meng Zhang, Bin Li & Wei Chen

  2. NHC Key Laboratory of Clinical Nephrology (Sun Yat-Sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, People’s Republic of China

    Siyang Ye, Meng Zhang, Bin Li & Wei Chen

  3. Division of Nephrology, Department of Medicine, The University of Hong Kong, Hong Kong, People’s Republic of China

    Sydney C. W. Tang

Authors
  1. Siyang Ye
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  2. Meng Zhang
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  3. Sydney C. W. Tang
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  4. Bin Li
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  5. Wei Chen
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Contributions

The study was conceptualized by SY, BL, and WC. Literature investigation and draft of the manuscript were performed by SY, MZ, and BL. WC and SCWT contributed to the revision of the manuscript.

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Correspondence to Bin Li or Wei Chen.

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Ye, S., Zhang, M., Tang, S.C.W. et al. PGC1-α in diabetic kidney disease: unraveling renoprotection and molecular mechanisms. Mol Biol Rep 51, 304 (2024). https://doi.org/10.1007/s11033-024-09232-y

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  • DOI: https://doi.org/10.1007/s11033-024-09232-y

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