Hepatocyte growth factor (HGF), HGF activator, and c-Met in synovial tissues in rheumatoid arthritis and osteoarthritis.
OBJECTIVE
Hepatocyte growth factor (HGF) is a multifunctional polypeptide that has been implicated in cancer growth, tissue development, and wound repair. Its actions are dependent on activation by HGF activator (HGFA) and its binding to a specific HGF receptor (c-Met). We examined the role of HGF, HGFA, and c-Met in synovial tissues in rheumatoid arthritis (RA) and osteoarthritis (OA), and their localization and mRNA expression.


METHODS
Immunohistochemical staining, Western blotting, RT-PCR, and in situ hybridization (ISH) for HGF, HGFA, and c-Met were performed on synovial tissue specimens from 10 patients with RA and 4 with OA, and 2 healthy controls.


RESULTS
Immunohistochemical staining revealed that HGFA and c-Met were strongly expressed in fibroblasts, macrophages, endothelial cells, and synovial lining cells. HGF was expressed only faintly in macrophages and fibroblasts, and not at all in the endothelial cells of RA and OA synovial tissue. HGFA was detected near 73 and 34 kDa on Western blot analysis, corresponding to inactive and active HGFA, respectively. RT-PCR showed HGF, HGFA, and c-Met mRNA in RA, OA, and control synovial tissue. ISH and immunohistochemistry revealed mRNA expression for HGF, HGFA, and c-Met in the cell types mentioned above.


CONCLUSIONS
HGFA, HGF, and c-Met mRNA are expressed in synovial tissue in RA and OA, and HGF is activated by HGFA and binds to c-Met on endothelial cells, inducing angiogenesis.
Nagashima
M
M
Department of Joint Disease and Rheumatism, Nippon Medical School, Tokyo, Japan. Nagashima_Masakazu/rheum@nms.ac.jp
Hasegawa
J
J
Kato
K
K
Yamazaki
J
J
Nishigai
K
K
Ishiwata
T
T
Asano
G
G
Yoshino
S
S
D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D015153:Blotting, Western; D017228:Hepatocyte Growth Factor / Q000032:analysis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D009389:Neovascularization, Pathologic / Q000378:metabolism; D010003:Osteoarthritis / Q000378:metabolism*; D019859:Proto-Oncogene Proteins c-met / Q000032:analysis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000032:analysis* / Q000235:genetics; D013583:Synovial Membrane / Q000737:chemistry / Q000502:physiology
D012333:RNA, Messenger; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; C081092:HGF activator; D012697:Serine Endopeptidases