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 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.