title: Increased phosphorylation of ezrin/radixin/moesin proteins contributes to proliferation of rheumatoid fibroblast-like synoviocytes.
abstract: OBJECTIVE
  Increasing evidence indicates that ezrin/radixin/moesin (ERM) proteins may play a critical role in cell proliferation. This study examined the role of ERM proteins in proliferation of fibroblast-like synoviocytes (FLS) from patients with RA.
  
  
  METHODS
  Synovial tissues (STs) were obtained from 18 RA and 6 OA patients. The expression of ERM and its phosphorylated proteins in cultured FLS and ST was assessed by western blots or IF staining. Small interference RNA (siRNA)-mediated ERM knockdown was used to inhibit phosphorylation of ERM. Proliferation of FLS was measured by bromodeoxyuridine (BrdU) incorporation into cell DNA and by PCNA immunoblotting.
  
  
  RESULTS
  Our study showed that increased phosphorylation of ERM proteins was found in ST and FLS from patients with RA as compared with OA patients and non-arthritis controls. Treatment with TNF-α, IL-1β or PDGF-induced phosphorylation of ERM proteins in dose- and time-dependent manner by RA FLS, but did not affect the expression of total ERM protein. Rho kinase and p38MAPK signal pathways were involved in TNF-α-induced ERM phosphorylation. We further showed that inhibition of ERM phosphorylation by siRNA-mediated ERM knockdown suppressed TNF-α- or IL-1β-induced BrdU incorporation and PCNA expression in RA FLS.
  
  
  CONCLUSIONS
  This study provides the novel evidence that increased phosphorylation of ERM proteins may contribute to proliferation of RA FLS, suggesting that specific inhibition of ERM phosphorylation may be a new therapeutic approach for RA.
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, PR China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Huang
authors.forename: Youjun
authors.initials: Y
authors.lastname: Xiao
authors.forename: Haobo
authors.initials: H
authors.lastname: Lin
authors.forename: Di
authors.initials: D
authors.lastname: Fu
authors.forename: Zhongping
authors.initials: Z
authors.lastname: Zhan
authors.forename: Liuqin
authors.initials: L
authors.lastname: Liang
authors.forename: Xiuyan
authors.initials: X
authors.lastname: Yang
authors.forename: Jinjin
authors.initials: J
authors.lastname: Fan
authors.forename: Yujin
authors.initials: Y
authors.lastname: Ye
authors.forename: Lin
authors.initials: L
authors.lastname: Sun
authors.forename: Hanshi
authors.initials: H
authors.lastname: Xu
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000473:pathology / Q000503:physiopathology; D015153:Blotting, Western; D016022:Case-Control Studies; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism*; D008875:Middle Aged; D010003:Osteoarthritis / Q000473:pathology / Q000503:physiopathology; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D012016:Reference Values; D012680:Sensitivity and Specificity; D013583:Synovial Membrane / Q000166:cytology* / Q000378:metabolism; D000099149:Ezrin
chemical_list: D016207:Cytokines; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D000099149:Ezrin; C071058:moesin; C071776:radixin