title: Glucose-6-phosphate isomerase promotes the proliferation and inhibits the apoptosis in fibroblast-like synoviocytes in rheumatoid arthritis.
abstract: BACKGROUND
  Fibroblast-like synoviocytes (FLS) play an important role in the pathogenesis of rheumatoid arthritis (RA). This study aimed to investigate the role of glucose 6-phosphate isomerase (GPI) in the proliferation of RA-FLS.
  
  
  METHODS
  The distribution of GPI in synovial tissues from RA and osteoarthritis (OA) patients was examined by immunohistochemical analysis. FLS were isolated and cultured, cellular GPI level was detected by real-time polymerase chain reaction (PCR) and Western blot analysis, and secreted GPI was detected by Western blot and enzyme-linked immunosorbent assay (ELISA). Doxorubicin (Adriamycin, ADR) was used to induce apoptosis. Cell proliferation was determined by MTS assay. Flow cytometry was used to detect cell cycle and apoptosis. Secreted pro-inflammatory cytokines were measured by ELISA.
  
  
  RESULTS
  GPI was abundant in RA-FLS and was an autocrine factor of FLS. The proliferation of both RA and OA FLS was increased after GPI overexpression, but was decreased after GPI knockdown. Meanwhile, exogenous GPI stimulated, while GPI antibody inhibited, FLS proliferation. GPI positively regulated its receptor glycoprotein 78 and promoted G1/S phase transition via extracellular regulated protein kinases activation and Cyclin D1 upregulation. GPI inhibited ADR-induced apoptosis accompanied by decreased Fas and increased Survivin in RA FLS. Furthermore, GPI increased the secretion of tumor necrosis factor-α and interleukin-1β by FLS.
  
  
  CONCLUSIONS
  GPI plays a pathophysiologic role in RA by stimulating the proliferation, inhibiting the apoptosis, and increasing pro-inflammatory cytokine secretion of FLS.
authors.affiliation: Department of Clinical Laboratory, Shanghai East Hospital, School of Medicine, Tong Ji University, 150 Ji Mo Road, Shanghai, 200120, People's Republic of China. billzong1318@126.com.
authors.forename: Ming
authors.initials: M
authors.lastname: Zong
authors.affiliation: Department of Clinical Laboratory, Shanghai East Hospital, School of Medicine, Tong Ji University, 150 Ji Mo Road, Shanghai, 200120, People's Republic of China. lutianbaodf@126.com.
authors.forename: Tianbao
authors.initials: T
authors.lastname: Lu
authors.affiliation: Department of Clinical Laboratory, Shanghai East Hospital, School of Medicine, Tong Ji University, 150 Ji Mo Road, Shanghai, 200120, People's Republic of China. tjfanshasha@126.com.
authors.forename: Shasha
authors.initials: S
authors.lastname: Fan
authors.affiliation: Department of Clinical Laboratory, Shanghai East Hospital, School of Medicine, Tong Ji University, 150 Ji Mo Road, Shanghai, 200120, People's Republic of China. zhanghuipcr@163.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Clinical Laboratory, Shanghai East Hospital, School of Medicine, Tong Ji University, 150 Ji Mo Road, Shanghai, 200120, People's Republic of China. gongruhan@yeah.net.
authors.forename: Ruhan
authors.initials: R
authors.lastname: Gong
authors.affiliation: Department of Clinical Laboratory, Shanghai East Hospital, School of Medicine, Tong Ji University, 150 Ji Mo Road, Shanghai, 200120, People's Republic of China. sunlishansh@163.com.
authors.forename: Lishan
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Clinical Laboratory, Shanghai East Hospital, School of Medicine, Tong Ji University, 150 Ji Mo Road, Shanghai, 200120, People's Republic of China. fuzhiyanlj@yeah.net.
authors.forename: Zhiyan
authors.initials: Z
authors.lastname: Fu
authors.affiliation: Department of Clinical Laboratory, Shanghai East Hospital, School of Medicine, Tong Ji University, 150 Ji Mo Road, Shanghai, 200120, People's Republic of China. flieying@yeah.net.
authors.forename: Lieying
authors.initials: L
authors.lastname: Fan
mesh_terms: D017209:Apoptosis / Q000502:physiology; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000473:pathology*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000502:physiology*; D002478:Cells, Cultured; D015331:Cohort Studies; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005347:Fibroblasts / Q000166:cytology; D005956:Glucose-6-Phosphate Isomerase / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D010003:Osteoarthritis / Q000276:immunology / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction; D018570:Risk Assessment; D012720:Severity of Illness Index; D013583:Synovial Membrane / Q000166:cytology
chemical_list: D018836:Inflammation Mediators; D005956:Glucose-6-Phosphate Isomerase