title: Resveratrol ameliorates hyperglycemia-induced renal tubular oxidative stress damage via modulating the SIRT1/FOXO3a pathway.
abstract: OBJECTIVE
  Oxidative stress plays an important role in the development and progression of diabetic nephropathy (DN). We aimed to investigate if resveratrol (RSV) could ameliorate hyperglycemia-induced oxidative stress in renal tubules via modulating the SIRT1/FOXO3a pathway.
  
  
  METHODS
  The effects of RSV on diabetes rats were assessed by periodic acid-Schiff, Masson staining, immunohistochemistry, and western blot analyses. Additionally, oxidative indicators (such as catalase, superoxide dismutase, reactive oxygen species, and malondialdehyde), the deacetylase activity of SIRT1 and protein expressions of SIRT1, FOXO3a, and acetylated-FOXO3a were measured. These indicators were similarly evaluated in an in vitro study. Furthermore, the silencing of SIRT1 was used to confirm its role in the resistance to oxidative stress and the relationship between SIRT1 and FOXO3a in vitro.
  
  
  RESULTS
  After 16weeks of RSV treatment, the renal function and glomerulosclerosis of rats with DN was dramatically ameliorated. RSV treatment increased SIRT1 deacetylase activity, subsequently decreasing the expression of acetylated-FOXO3a and inhibiting the oxidative stress caused by hyperglycemia both in vivo and in vitro. The silencing of SIRT1 in HK-2 cells aggravated the high glucose-induced oxidative stress and overexpression of acetylated-FOXO3a; RSV treatment failed to protect against these effects.
  
  
  CONCLUSIONS
  RSV modulates the SIRT1/FOXO3a pathway by increasing SIRT1 deacetylase activity, subsequently ameliorating hyperglycemia-induced renal tubular oxidative stress damage. This mechanism provides the basis for a new approach to developing an effective DN treatment, which is of great clinical significance for reducing the morbidity and mortality associated with DN.
authors.affiliation: Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Jinan, Shandong, China.
authors.forename: Xueling
authors.initials: X
authors.lastname: Wang
authors.affiliation: Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Jinan, Shandong, China.
authors.forename: Linghang
authors.initials: L
authors.lastname: Meng
authors.affiliation: Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Jinan, Shandong, China.
authors.forename: Long
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Anesthesia Department, Shengli Oilfield Central Hospital, Dongying, Shandong, China.
authors.forename: Zengfu
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Jinan, Shandong, China.
authors.forename: Haiying
authors.initials: H
authors.lastname: Liu
authors.affiliation: Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Jinan, Shandong, China. Electronic address: lg69007@163.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.affiliation: Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Jinan, Shandong, China. Electronic address: guangj@sdu.edu.cn.
authors.forename: Guangju
authors.initials: G
authors.lastname: Guan
mesh_terms: D000818:Animals; D002374:Catalase / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects; D003928:Diabetic Nephropathies / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000071316:Forkhead Box Protein O3 / Q000378:metabolism; D006943:Hyperglycemia / Q000150:complications* / Q000378:metabolism*; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D056564:Sirtuin 1 / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: C499515:FOXO3 protein, rat; D000071316:Forkhead Box Protein O3; D017382:Reactive Oxygen Species; D013267:Stilbenes; D002374:Catalase; D013482:Superoxide Dismutase; D056564:Sirtuin 1; D000077185:Resveratrol
keywords: Deacetylation; Diabetic nephropathy; FOXO3a; Oxidative stress; Resveratrol; SIRT1