Renal Protective Effect of Sirtuin 1

Dong, Yijun; Liu, Nian; Xiao, Zhi; Sun, Tao; Wu, Shu-Hui; Sun, Weixia; Xu, Zhenhe; Yuan, Hang

doi:10.1155/2014/843786

Cited by 64 publications

(55 citation statements)

References 55 publications

(57 reference statements)

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“…Emerging evidence has suggested that SIRT1 expresses in medullary tubular cells, and protects and maintains kidney cell function [17]. Our present study found that treatment of IMCD cells with TNF-α significantly decreased SIRT1 expression at mRNA and protein levels in a time-and concentration-dependent manner.…”

Section: Discussionsupporting

confidence: 67%

Sirtuin1 (SIRT1) Regulates Tumor Necrosis Factor-alpha (TNF-α-Induced) Aquaporin-2 (AQP2) Expression in Renal Medullary Collecting Duct Cells Through Inhibiting the NF-κB Pathway

Lin¹,

Geng²,

Lin³

et al. 2016

Med Sci Monit Basic Res

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BackgroundAquaporin-2 (AQP2) plays a major role in water reabsorption in the renal collecting duct, and is involved in a variety of renal disease. Recent studies have indicate that sirtuin1 (SIRT1) exerts renoprotective properties against kidney diseases. This study aimed to determine the potential role of SIRT1 in AQP2 expression induced by tumor necrosis factor-alpha (TNF-α) and to disclose the underlying mechanism in renal inner medullary collecting duct (IMCD) cells.Material/MethodsQuantitative real-time PCR and Western blotting were respectively identified mRNA and protein expression. Immunofluorescence staining was used to detect the localization of AQP2. Small-interfering RNA (siRNA) was carried out for mechanism study.ResultsResults showed that AQP2 was clearly increased in the plasma membrane and decreased in the cytoplasm of IMCD cells treated with AVP. TNF-α treatment in IMCD cells significantly reduced SIRT1 and AQP2 expression, and increased acetylated NF-κBp65 protein level in time- and concentration-dependent manners. Moreover, SIRT1 overexpression or the activator SRT1720 augmented AQP2 expression and reduced the acetylation of NF-κBp65, which was reversed by SIRT1 siRNA or the inhibitors Ex527 and sirtinol in TNF-α-induced IMCD cells. Knockdown of NF-κBp65 or NF-κBp65 inhibition by pyrrolidine dithiocarbamate (PDTC) enhanced AQP2 expression in IMCD cells exposed to TNF-α. Importantly, knockdown of NF-κBp65 augmented the up-regulation of SIRT1 on AQP2 expression in IMCD cells induced by TNF-α.ConclusionsThese findings indicate that SIRT1 increases AQP2 expression in TNF-α-induced IMCD cells via the NF-κB-dependent signalling pathway, which might provide novel insight to understanding the renoprotective effects of SIRT1 in kidney diseases.

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Section: Discussionsupporting

confidence: 67%

Sirtuin1 (SIRT1) Regulates Tumor Necrosis Factor-alpha (TNF-α-Induced) Aquaporin-2 (AQP2) Expression in Renal Medullary Collecting Duct Cells Through Inhibiting the NF-κB Pathway

Lin¹,

Geng²,

Lin³

et al. 2016

Med Sci Monit Basic Res

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“…25 From a translational perspective, it needs to be considered that pharmacologic inhibition of Sirt1 can also elicit pro-inflammatory effects, and potentially also nephrotoxic effects, which may worsen the renal allograft outcome. 26 Sirt1 deacetylates p65 at K310, and, loss of Sirt1 function can lead to increased inflammation especially in myeloid cells. 27, 28 In the kidney, Sirt1 can act protectively during ischemia/reperfusion injury by stimulating mitochondrial biogenesis and reducing inflammation.…”

Section: Discussionmentioning

confidence: 99%

Targeting Sirtuin-1 prolongs murine renal allograft survival and function

Levine

Wang

Xiao

et al. 2016

Kidney International

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Current immunosuppressive medications used after transplantation have significant toxicities. Foxp3+ T-regulatory (Treg) cells can prevent allograft rejection without compromising protective host immunity. Interestingly, inhibiting the class III histone/protein deacetylase Sirtuin-1 can augment Foxp3+ Treg suppressive function through increasing Foxp3 acetylation. Here we determined whether Sirtuin-1 targeting can stabilize biological allograft function. BALB/c kidney allografts were transplanted into C57BL/6 recipients with a CD4-conditional deletion of Sirtuin-1 (Sirt1fl/flCD4cre) or mice treated with a Sirtuin-1 specific inhibitor (EX-527), and the native kidneys removed. Blood chemistries and hematocrit were followed weekly. Sirt1fl/flCD4cre recipients showed markedly longer survival and improved kidney function. Sirt1fl/flCD4cre recipients exhibited donor specific tolerance, accepted BALB/c, but rejected third-party C3H cardiac allografts. C57BL/6 recipients of BALB/c renal allografts that were treated with EX-527 showed improved survival and renal function at 1, but not 10 mg/kg/day. Pharmacologic inhibition of Sirtuin-1 also improved renal allograft survival and function with dosing effects having relevance to outcome. Thus, inhibiting Sirtuin-1 can be a useful asset in controlling T-cell mediated rejection. However, effects on non-T cells that could adversely affect allograft survival and function merit consideration.

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“…Tubular cell apoptosis is one of the tubular atrophy mechanism, which could result in ESRD. 2,9 Activation of SIRT1 alleviated DN by reducing renal cell apoptosis, relieving renal inflammation and fibrosis. 4 Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase acting as a central regulator in the signalling pathway involving in the control of cell growth, proliferation, and metabolism.…”

Section: Introductionmentioning

confidence: 99%

“…3 Hyperglycaemia in kidney also causes morphological changes, including glomerular hypertrophy, basement membrane thickening, and the accumulation of mesangial matrix. 1,9 Adiponectin (APN), an adipocyte-derived hormone, is a 30-KDa polypeptide with 244 amino acids 10,11 participating in the protection of different organs against oxidative stress. 5 mTOR pathway is essential for podocyte homeostasis.…”

Section: Introductionmentioning

confidence: 99%

Prevention of kidney cell damage in hyperglycaemia condition by adiponectin

Esmaeili

Motamedrad

Hemmati

et al. 2019

Cell Biochemistry & Function

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Adiponectin (APN) is an adipocytokine, secreted from adipose tissue and has antiinflammatory, anti-ageing, and antidiabetic properties. Hyperglycaemia can damage the renal cells, and mammalian target of rapamycin (mTOR), along with Sirtuin 1 (SIRT1), have an important role in kidney cell response to hyperglycaemia. Therefore, understanding the relationship between adiponectin, mTOR, and SIRT1 proteins is beneficial for deciphering the mechanism of adiponectin function. In this study, Human Embryonic Kidney-293 (HEK-293) cells were cultured under normal and high-glucose condition, with and without APN (1, 10, and 100 ng/mL) for 48 hours. mTOR protein expression was evaluated by western blot analysis, and SIRT1 protein was assessed using ELISA method. To evaluate hyperglycaemia-mediated cytotoxicity, cell viability was determined using MTT assay. Data showed that APN in high dose (100 ng/mL) significantly reduced the expression of mTOR and p-mTOR, increased SIRT1 protein, and also improved cell viability compared with the control high glucose (p ≤ 0.05). According to this results, APN can be useful in preventing renal cell damage, by affecting on the expression of mTOR and SIRT1 proteins, as well as increasing the survival of kidney cells in hyperglycaemia conditions. Significance of the study: Adiponectin triggered mTOR/p-mTOR/SIRT1 pathway and decreased cell death in human kidney cells. Our findings provide preliminary experimental data that support further studies on the potential therapeutic role of adiponectin in diabetes and diabetic-induced metabolic complications.

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Renal Protective Effect of Sirtuin 1

Cited by 64 publications

References 55 publications

Sirtuin1 (SIRT1) Regulates Tumor Necrosis Factor-alpha (TNF-α-Induced) Aquaporin-2 (AQP2) Expression in Renal Medullary Collecting Duct Cells Through Inhibiting the NF-κB Pathway

Sirtuin1 (SIRT1) Regulates Tumor Necrosis Factor-alpha (TNF-α-Induced) Aquaporin-2 (AQP2) Expression in Renal Medullary Collecting Duct Cells Through Inhibiting the NF-κB Pathway

Targeting Sirtuin-1 prolongs murine renal allograft survival and function

Prevention of kidney cell damage in hyperglycaemia condition by adiponectin

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