title: Sirt1 is essential for resveratrol enhancement of hypoxia-induced autophagy in the type 2 diabetic nephropathy rat.
abstract: Type 2 diabetic nephropathy (DN) is a serious end-stage kidney disease worldwide. Multiple studies demonstrate that resveratrol (RSV) has a beneficial effect on DN. However, whether RSV-induced improvement in kidney function in diabetes is due to the regulation of autophagy remains unclear. Here, we investigated the mechanisms underlying RSV-mediated protection against DN in diabetic rats, with a special focus on the role of NAD-dependent deacetylase sirtuin 1 (Sirt1) in regulating autophagy. We found that long-term RSV treatment in rats promoted Sirt1 expression and improved related metabolic levels in the diabetic kidney. Our study showed that, in cultured NRK-52E cells, Sirt1 knockdown inhibited the autophagy levels of proteins Atg7, Atg5, and LC3 and impaired the RSV amelioration of dysfunctional autophagy under hypoxic condition. Furthermore, exposed to 1% O2 over time induced autophagy dysfunction and apoptosis in NRK-52E cells, which could be improved by RSV treatment. Our data highlight the role of the Sirt1-mediated pathway in the effects of RSV on autophagy in vivo and in vitro, suggesting RSV could be a potential new therapy for type 2 DN.
authors.affiliation: Department of Nephrology, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157 Xiwu Rd., 710004 Xi'an, Shaanxi Province, China.
authors.forename: Liqun
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Nephrology, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157 Xiwu Rd., 710004 Xi'an, Shaanxi Province, China.
authors.forename: Rongguo
authors.initials: R
authors.lastname: Fu
authors.affiliation: Department of Nephrology, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157 Xiwu Rd., 710004 Xi'an, Shaanxi Province, China.
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Duan
authors.affiliation: Department of Nephrology, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157 Xiwu Rd., 710004 Xi'an, Shaanxi Province, China.
authors.forename: Jiamei
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Nephrology, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157 Xiwu Rd., 710004 Xi'an, Shaanxi Province, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Nephrology, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157 Xiwu Rd., 710004 Xi'an, Shaanxi Province, China.
authors.forename: Lifang
authors.initials: L
authors.lastname: Tian
authors.affiliation: Department of Nephrology, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157 Xiwu Rd., 710004 Xi'an, Shaanxi Province, China.
authors.forename: Zhian
authors.initials: Z
authors.lastname: Lv
authors.affiliation: Department of Nephrology, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157 Xiwu Rd., 710004 Xi'an, Shaanxi Province, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Nephrology, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157 Xiwu Rd., 710004 Xi'an, Shaanxi Province, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Nephrology, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157 Xiwu Rd., 710004 Xi'an, Shaanxi Province, China.
authors.forename: Lining
authors.initials: L
authors.lastname: Jia
authors.affiliation: Department of Nephrology, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157 Xiwu Rd., 710004 Xi'an, Shaanxi Province, China. Electronic address: wanglieryuan@126.com.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects* / Q000502:physiology; D015153:Blotting, Western; D015687:Cell Hypoxia / Q000187:drug effects; D002460:Cell Line; D003921:Diabetes Mellitus, Experimental; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D055785:Gene Knockdown Techniques; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D020133:Reverse Transcriptase Polymerase Chain Reaction; D056564:Sirtuin 1 / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D013267:Stilbenes; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; D000077185:Resveratrol
keywords: Autophagy; Diabetic nephropathy; Hypoxia; Resveratrol; Sirt1