Role of sirtuin-1 in diabetic nephropathy

Wang, Wanning; Sun, Weixia; Cheng, Yiyun; Xu, Zhenhe; Cai, Lu

doi:10.1007/s00109-019-01743-7

Cited by 103 publications

(79 citation statements)

References 152 publications

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“…Diet restriction intervention could improve the autophagy function of the kidney and alleviate kidney damage caused by diabetes mellitus. This process is regulated by silent mating type information regulation 2 homolog 1 (Sirtl) . Sirt1 is a NAD + dependent deacetylase and an important regulator of FOXO1 transcriptional function.…”

Section: Introductionmentioning

confidence: 99%

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Metformin alleviates renal injury in diabetic rats by inducing Sirt1/FoxO1 autophagic signal axis

Liu

et al. 2020

Clin Exp Pharma Physio

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Diabetic nephropathy (DN) is the major microvascular complication of diabetes mellitus and the most important cause of end‐stage renal disease worldwide. Metformin is the preferred oral hypoglycaemic drug for type 2 diabetes mellitus (T2DM). Recent studies have shown that besides lowering blood glucose, metformin also has protective effects on renal function, but its mechanism is not clear. In this study, we established a diabetic rat model by high‐fat feeding combined with intraperitoneal injection of streptozotocin. Their changes of renal function, oxidative stress, histopathology and structure, and autophagy were observed after 8 weeks of metformin treatment at different dose. Sirt1 inhibitor EX527 and metformin were used to observe whether the protective effect of metformin on DN kidney was achieved through the Sirt1/FoxO1 autophagic signalling pathway. The results showed that metformin could protect renal function by up‐regulating autophagy level, alleviating oxidative stress level of renal tissue and pathological and structural changes of glomeruli, and inhibiting the expression of extracellular matrix. Sirt1 inhibitor could block the protective effect of metformin on kidney of diabetic rats, suggesting that metformin could alleviate kidney injury in diabetic rats by inducing Sirt1/FoxO1 autophagy signal axis. So metformin could alleviate renal injury in diabetic rats, which may be achieved by regulating Sirt1/FoxO1 autophagic signalling pathway and inducing renal autophagy.

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Section: Introductionmentioning

confidence: 99%

“…This process is regulated by silent mating type information regulation 2 homolog 1 (Sirtl). 10 Sirt1 is a NAD + dependent deacetylase and an important regulator of FOXO1 transcriptional function. It can regulate FOXO1 through deacetylation, promote its expression and enhance its transcriptional activity.…”

mentioning

confidence: 99%

Metformin alleviates renal injury in diabetic rats by inducing Sirt1/FoxO1 autophagic signal axis

Liu

et al. 2020

Clin Exp Pharma Physio

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“…Although DN pathogenesis has made progress, its high incidence and poor prognosis have not been greatly improved [19]. Therefore, excavating novel therapeutic targets for DN is significant.…”

Section: Discussionmentioning

confidence: 99%

MiR-770-5p facilitates podocyte apoptosis and inflammation in diabetic nephropathy by targeting TIMP3

Wang

2020

Bioscience Reports

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Objective: Diabetic nephropathy (DN) is one of the most severe and frequent diabetic complications. MicroRNAs (miRNAs) have been reported to play a vital role in DN pathogenesis. The present study aimed to investigate the molecular mechanism of miR-770-5p in DN. Methods: Podocyte injury model was established by treating mouse podocytes with high glucose (HG, 33 mM) for 24 h. The levels of miR-770-5p and TIMP3 were examined in kidney tissues and podocytes using quantitative real-time PCR (qRT-PCR). Flow cytometry analysis was applied to detect apoptosis in podocytes. Western blot assay was used to measure the protein levels of B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X (Bax) and tissue inhibitors of metalloproteinase 3 (TIMP3). Enzyme-linked immunosorbent assay (ELISA) was conducted to measure the levels of inflammatory factors. The interaction between miR-770-5p and TIMP3 was determined by MicroT-CDS and luciferase reporter assay. Results: MiR-770-5p was up-regulated and TIMP3 was down-regulated in DN kidney tissues and HG-stimulated podocytes. Depletion of miR-770-5p suppressed cell apoptosis and the release of pro-inflammatory factors in HG-treated podocytes. Additionally, TIMP3 was a target of miR-770-5p in HG-treated podocytes. TIMP3 inhibited cell apoptosis and inflammation in HG-treated podocytes. Moreover, TIMP3 knockdown alleviated the inhibitory effect of miR-770-5p silencing on podocyte apoptosis and inflammatory response. Conclusion: Knockdown of miR-770-5p suppressed podocyte apoptosis and inflammatory response by targeting TIMP3 in HG-treated podocytes, indicating that miR-770-5p may be a potential therapeutic target for DN therapy.

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“…One previous study suggested that SIRT1 decreased activation of NLRP3 inflammasome in vitro [10]. Furthermore, SIRT1 was found to preserve podocyte function by regulating claudin-1, which induces podocyte effacement and albuminuria [46,47]. Hence, the AMPK/SIRT1 signaling pathway could be a therapeutic target in diabetic kidney damage.…”

Section: Discussionmentioning

confidence: 99%

Lespedeza bicolor Extract Ameliorated Renal Inflammation by Regulation of NLRP3 Inflammasome-Associated Hyperinflammation in Type 2 Diabetic Mice

Park¹,

Lee²,

Kim³

et al. 2020

Antioxidants

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Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia. The chronic hyperglycemic condition causes hyperinflammation via activation of nucleotide-binding oligomerization domain-like pyrin domain containing receptor 3 (NLRP3) inflammasome and abnormally leads to morphological and functional changes in kidney. A previous study showed a protective effect of Lespedeza bicolor extract (LBE) on endothelial dysfunction induced by methylglyoxal glucotoxicity. We aimed to investigate whether LBE ameliorated renal damage through regulation of NLRP3 inflammasome-dependent hyper-inflammation in T2DM mice. After T2DM induction by a high fat diet and low dose of streptozotocin (30 mg/kg), the mice were administered with different dosages of LBE (100 or 250 mg/kg/day) by gavage for 12 weeks. LBE supplementation ameliorated kidney dysfunction demonstrated by urine albumin-creatinine at a low dose and plasma creatinine, blood urea nitrogen (BUN), and glomerular hypertrophy at a high dose. Furthermore, a high dose of LBE supplementation significantly attenuated renal hyper-inflammation associated with NLRP3 inflammasome and oxidative stress related to nuclear factor erythroid 2-related factor 2 (Nrf-2) in T2DM mice. Meanwhile, a low dose of LBE supplementation up-regulated energy metabolism demonstrated by phosphorylation of adenosine monophosphate kinase (AMPK) and Sirtuin (SIRT)-1 in T2DM mice. In conclusion, the current study suggested that LBE, in particular, at a high dose could be used as a beneficial therapeutic for hyperglycemia-induced renal damage in T2DM.

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Role of sirtuin-1 in diabetic nephropathy

Cited by 103 publications

References 152 publications

Metformin alleviates renal injury in diabetic rats by inducing Sirt1/FoxO1 autophagic signal axis

Metformin alleviates renal injury in diabetic rats by inducing Sirt1/FoxO1 autophagic signal axis

MiR-770-5p facilitates podocyte apoptosis and inflammation in diabetic nephropathy by targeting TIMP3

Lespedeza bicolor Extract Ameliorated Renal Inflammation by Regulation of NLRP3 Inflammasome-Associated Hyperinflammation in Type 2 Diabetic Mice

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