M. Nagashima et al., Hepatocyte growth factor (HGF), HGF activator, and c-Met in synovial tissues in rheumatoid arthritis and osteoarthritis, J RHEUMATOL, 28(8), 2001, pp. 1772-1778
Objective. Hepatocyte growth factor (HGF) is a multifunctional polypeptide
that has been implicated in cancer growth, tissue development, and wound re
pair. Its actions are dependent on activation by HGF activator (HGFA) and i
ts 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 osteo
arthritis (OA), and their localization and mRNA expression.
Methods. Immunohistochemical staining, Western blotting, RT-PCR, and in sit
u hybridization (ISH) for HGF, HGFA, and c-Met were performed on synovial t
issue specimens from 10 patients with RA and 4 with OA, and 2 healthy contr
ols.
Results. Immunohistochemical staining revealed that HGFA and c-Met were str
ongly expressed in fibroblasts, macrophages, endothelial cells, and synovia
l lining cells. HGF was expressed only faintly in macrophages and fibroblas
ts, and not at all in the endothelial cells of RA and OA synovial tissue. H
GFA 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 immunohistochemist
ry revealed mRNA expression for HGF, HGFA, and c-Met in the cell types ment
ioned above.
Conclusion. HGFA, HGF, and c-Met mRNA are expressed in synovial tissue in R
A and OA, and HGF is activated by HGFA and binds to c-Met on endothelial ce
lls, inducing angiogenesis.