title: Fluvastatin inhibits the expression of fibronectin in human peritoneal mesothelial cells induced by high-glucose peritoneal dialysis solution via SGK1 pathway.
abstract: BACKGROUND
  Previous studies showed that statins may have protective effects on peritoneal mesothelial cells (PMC) cultured in high glucose. However, the mechanisms are not clear yet. Several studies demonstrated that serum- and glucocorticoid-inducible kinase 1 (SGK1) is implicated in tissue fibrosis of liver, lung and kidney by regulating the expression of many profibrogenic cytokines and extracellular matrix (e.g., fibronectin). However, few available reports elucidated whether the SGK1 is involved in the pathogenesis of peritoneal fibrosis (PF) in patients with peritoneal dialysis (PD). So far, there is no study about the interaction between the statins and SGK1 in PMC. The purpose of this study was to identify whether fluvastatin may decrease the expression of fibronectin (FN) in human peritoneal mesothelial cells (HPMC) cultured with high-glucose peritoneal dialysis solution (HGPDS) by affecting SGK1 signal pathway.
  
  
  METHODS
  Cultured HPMC were divided into groups of control, high-glucose peritoneal dialysis solution (HGPDS), HGPDS with fluvastatin (10(-8) mol/L ~ 10(-6) mol/L) or GSK650394 10(-5) mol/L (the competitive inhibitor of SGK1), fluvastatin 10(-6) mol/L or GSK650394 10(-5) mol/L alone. The expression of SGK1 and FN was detected by RT-PCR, western immunoblotting or ELISA.
  
  
  RESULTS
  Compared with the control, the mRNA and protein expression of SGK1 and FN increased significantly in HPMC treated with HGPDS (p < 0.05). GSK650394 significantly decreased the upregulated mRNA and protein expression of SGK1 and FN induced by HGPDS (p < 0.05), and fluvastatin had the same effects as GSK650394 in a dose-dependent manner (p < 0.05).
  
  
  CONCLUSIONS
  Expression of SGK1 and FN increased in HPMC induced by HGPDS. Treated with fluvastatin and the SGK1-inhibitor GSK650394, abnormalities of SGK1 and FN could be corrected partially, which suggested that the SGK1 pathway was implicated in the pathogenesis of PF, and that fluvastatin might decrease the expression of SGK1 so as to meliorate the progression of PF.
authors.affiliation: Department of Nephrology, First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China. jiajj3@sina.com.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Nephrology, First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China.
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Nephrology, First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China.
authors.forename: Yaguang
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Nephrology, First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China.
authors.forename: Xiufen
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Nephrology, First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Qian
authors.affiliation: Department of Nephrology, First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Sun
authors.affiliation: Department of Nephrology, First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China.
authors.forename: Changying
authors.initials: C
authors.lastname: Xing
mesh_terms: D001565:Benzoates / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002478:Cells, Cultured; D015314:Dialysis Solutions / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D005229:Fatty Acids, Monounsaturated / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism*; D000077340:Fluvastatin; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D007211:Indoles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010537:Peritoneum / Q000166:cytology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D001565:Benzoates; D019086:Bridged Bicyclo Compounds, Heterocyclic; D015314:Dialysis Solutions; D005229:Fatty Acids, Monounsaturated; D005353:Fibronectins; D000077340:Fluvastatin; D005947:Glucose; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017874:Immediate-Early Proteins; D007211:Indoles; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D000099184:Serum-Glucocorticoid Regulated Kinases; C532254:2-cyclopentyl-4-(5-phenyl-1H-pyrrolo(2,3-b)pyridin-3-yl)-benzoic acid
keywords: Fibronectin; Fluvastatin; High-glucose peritoneal dialysis solution; Human peritoneal mesothelial cells; Serum- and glucocorticoid-inducible kinase 1