title: Role of moesin in renal fibrosis.
abstract: BACKGROUND
  Renal fibrosis is the final common pathway of chronic kidney disease (CKD). Moesin is a member of Ezrin/Radixin/Moesin (ERM) protein family but its role in renal fibrosis is not clear.
  
  
  METHODS
  Human proximal tubular cells (HK-2) were stimulated with or without TGF-β1. Moesin and downstream target genes were examined by real-time PCR and western blot. Phosphorylation of moesin and related signaling pathway was investigated as well. Rat model of unilateral ureteral obstruction (UUO) was established and renal moesin was examined by immunohistochemistry. Moesin in HK-2 cells were knocked down by siRNA and change of downstream genes in transfected HK-2 cells was studied. All animal experiments were reviewed and approved by the Ethics Committee for animal care of Ruijin Hospital.
  
  
  RESULTS
  HK-2 cells stimulated with TGF-β1 showed up-regulated level of α-SMA and down-regulated level of E-Cadherin as well as elevated mRNA and protein level of moesin. In rat model of UUO, renal moesin expression increased in accordance with severity of tubulointerestital fibrosis in the kidneys with ureteral ligation while the contralateral kidneys were normal. Further study showed that TGF-β1 could induce phosphorylation of moesin which depended on Erk signaling pathway and Erk inhibitor PD98059 could block moesin phosphorylation. Effects of TGF-β1 on moesin phosphorylation was prior to its activation to total moesin. RNA silencing studies showed that knocking down of moesin could attenuate decrease of E-Cadherin induced by TGF-β1.
  
  
  CONCLUSIONS
  We find that moesin might be involved in renal fibrosis and its effects could be related to interacting with E-Cadherin.
authors.affiliation: Department of nephrology, Ruijin Hospital, Shanghai Jiaotong University, school of medicine, Shanghai, PR China.
authors.forename: Yong-Xi
authors.initials: YX
authors.lastname: Chen
authors.affiliation: Department of nephrology, Ruijin Hospital, Shanghai Jiaotong University, school of medicine, Shanghai, PR China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of nephrology, Ruijin Hospital, Shanghai Jiaotong University, school of medicine, Shanghai, PR China.
authors.forename: Wei-Ming
authors.initials: WM
authors.lastname: Wang
authors.affiliation: Department of nephrology, Ruijin Hospital, Shanghai Jiaotong University, school of medicine, Shanghai, PR China.
authors.forename: Xia-Lian
authors.initials: XL
authors.lastname: Yu
authors.affiliation: Department of nephrology, Ruijin Hospital, Shanghai Jiaotong University, school of medicine, Shanghai, PR China.
authors.forename: Yi-Mei
authors.initials: YM
authors.lastname: Wang
authors.affiliation: Animal Experiment and Research Center, Ruijin Hospital, Shanghai Jiaotong University, school of medicine, Shanghai, PR China.
authors.forename: Min-Jun
authors.initials: MJ
authors.lastname: Zhang
authors.affiliation: Department of nephrology, Ruijin Hospital, Shanghai Jiaotong University, school of medicine, Shanghai, PR China.
authors.forename: Nan
authors.initials: N
authors.lastname: Chen
mesh_terms: D000199:Actins / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism*; D002460:Cell Line; D005355:Fibrosis / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008840:Microfilament Proteins / Q000378:metabolism*; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D051436:Renal Insufficiency, Chronic / Q000378:metabolism* / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D053773:Transforming Growth Factor beta1
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D015820:Cadherins; D008840:Microfilament Proteins; D034741:RNA, Small Interfering; D053773:Transforming Growth Factor beta1; C071058:moesin