title: Serum response factor accelerates the high glucose-induced Epithelial-to-Mesenchymal Transition (EMT) via snail signaling in human peritoneal mesothelial cells.
abstract: BACKGROUND
  Epithelial-to-Mesenchymal Transition (EMT) induced by glucose in human peritoneal mesothelial cells (HPMCs) is a major cause of peritoneal membrane (PM) fibrosis and dysfunction.
  
  
  METHODS
  To investigate serum response factor (SRF) impacts on EMT-derived fibrosis in PM, we isolated HPMCs from the effluents of patients with end-stage renal disease (ESRD) to analyze alterations during peritoneal dialysis (PD) and observe the response of PM to SRF in a rat model.
  
  
  RESULTS
  Our results demonstrated the activation and translocation of SRF into the nuclei of HPMCs under extensive periods of PD. Accordingly, HPMCs lost their epithelial morphology with a decrease in E-cadherin expression and an increase in α-smooth muscle actin (α-SMA) expression, implying a transition in phenotype. PD with 4.25% glucose solution significantly induced SRF up-regulation and increased peritoneal thickness. In immortal HPMCs, high glucose (HG, 60 mmol/L) stimulated SRF overexpression in transformed fibroblastic HPMCs. SRF-siRNA preserved HPMC morphology, while transfection of SRF plasmid into HPMCs caused the opposite effects. Evidence from electrophoretic mobility shift, chromatin immunoprecipitation and reporter assays further supported that SRF transcriptionally regulated Snail, a potent inducer of EMT, by directly binding to its promoter.
  
  
  CONCLUSIONS
  Our data suggested that activation of SRF/Snail pathway might contribute to the progressive PM fibrosis during PD.
authors.affiliation: Department of Nephrology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaan xi, China; State Key Laboratory of Cancer Biology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaan xi, China.
authors.forename: Lijie
authors.initials: L
authors.lastname: He
authors.affiliation: Department of Nephrology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaan xi, China; State Key Laboratory of Cancer Biology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaan xi, China.
authors.forename: Weijuan
authors.initials: W
authors.lastname: Lou
authors.affiliation: Department of Nephrology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaan xi, China; State Key Laboratory of Cancer Biology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaan xi, China; Department of Nephrology, Xingyuan Hospital, the Fourth Hospital of Yulin, Yulin, Shaan xi, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Ji
authors.affiliation: Department of Nephrology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaan xi, China; State Key Laboratory of Cancer Biology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaan xi, China; Department of Nephrology, the Ninth Hospital of Xi'an, Xi'an, Shaan xi, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liang
authors.affiliation: Department of Nephrology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaan xi, China.
authors.forename: Meilan
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Department of Nephrology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaan xi, China.
authors.forename: Guoshang
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Nephrology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaan xi, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Nephrology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaan xi, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Nephrology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaan xi, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Nephrology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaan xi, China; State Key Laboratory of Cancer Biology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaan xi, China.
authors.forename: Hanmin
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Nephrology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaan xi, China; Department of Nephrology, State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital and Medical College, Beijing, China.
authors.forename: Xiangmei
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Nephrology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaan xi, China; State Key Laboratory of Cancer Biology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaan xi, China.
authors.forename: Shiren
authors.initials: S
authors.lastname: Sun
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D058750:Epithelial-Mesenchymal Transition; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000628:therapy; D008297:Male; D010530:Peritoneal Dialysis; D056627:Peritoneal Fibrosis / Q000378:metabolism* / Q000473:pathology; D010537:Peritoneum / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D026362:Serum Response Factor / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D026362:Serum Response Factor; D005947:Glucose