title: Mir-217 promotes inflammation and fibrosis in high glucose cultured rat glomerular mesangial cells via Sirt1/HIF-1α signaling pathway.
abstract: Silent information regulator 1 (Sirt1) plays a protective role in kidney. Sirt1 suppresses activation of hypoxia-inducible factor-1 alpha (HIF-1α), with MircroRNA-217 (Mir-217) being closely related to Sirt1. The relationship of Sirt1, HIF-1α and Mir-217, however, has never been reported in high glucose cultured rat glomerular mesangial cells (RMCs). Thus, we explored the role of Mir-217 on inflammation and fibrosis in RMCs cultured with high glucose in vitro through Sirt1/HIF-1α signaling pathway.
  
  
  
  Rat glomerular mesangial cells were pre-incubated with Sirt1 activator Resveratrol prior to high glucose treatment. Furthermore the cells were transiently transfected with Sirt1 small interfering RNA (siRNA), HIF-1α siRNA and Mir-217 inhibitor using Lipofectamine 2000. Real-time PCR was used to analyse the expression of Mir-217, Sirt1 mRNA and HIF-1α mRNA; Western Blot was used to observe protein expression of Sirt1, HIF-1α, connective tissue growth factor, endothelin-1 and fibronectin; enzyme-linked immunosorbent assay was used to detect protein expression of transforming growth factor-β1 and vascular endothelial growth factor.
  
  
  
  High glucose increased Mir-217 expression. High glucose decreased Sirt1 expression, accompanied by the increased HIF-1α expression and then promoted inflammation and fibrosis. In addition, Mir-217 gene silencing or Resveratrol could suppress the expression of HIF-1α, which in turn restrained inflammation and fibrosis in rat glomerular mesangial cells cultured with high glucose.
  
  
  
  This study clarified the role of Mir-217 in high glucose cultured rat glomerular mesangial cells through Sirt1/HIF-1α signaling pathway and provided new therapeutic targets for diabetic nephropathy. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Department of Endocrinology, the First Hospital Affiliated to China Medical University, Shenyang, Liaoning, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Shao
authors.affiliation: Department of Endocrinology, the First Hospital Affiliated to China Medical University, Shenyang, Liaoning, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Lv
authors.affiliation: Department of Endocrinology, the First Hospital Affiliated to China Medical University, Shenyang, Liaoning, China.
authors.forename: Can
authors.initials: C
authors.lastname: Wu
authors.affiliation: Division of Endocrinology, Shenyang NO.8 hospital, Shenyang, Liaoning, China.
authors.forename: Yuehong
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Endocrinology, the First Hospital Affiliated to China Medical University, Shenyang, Liaoning, China.
authors.forename: Qiuyue
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005355:Fibrosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D050527:Mesangial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D013549:Sweetening Agents / Q000494:pharmacology
chemical_list: C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C000623105:MIRN217 microRNA, rat; D035683:MicroRNAs; D013549:Sweetening Agents; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; D005947:Glucose
keywords: diabetic nephropathy; hypoxia-inducible factor-1α; microRNA; microRNA-217; silent information regulator 1