Hepatocyte growth factor [HGF], HGF activator [HGFA] and c-met expression in rheumatoid synovial tissues in relation to disease activity

ABSTRACT

We examined the localization and mRNA expression of HGF, HGFA and c-Met in synovial tissues [ST] in rheumatoid arthritis [RA] in relation to disease activity to characterize its biologic function in that disease. Immunohistochemical staining and RT-PCRfor HGF, HGFA and c-Met were performed on ST specimens from 34 RA-patients and 20 osteoarthritis [OA] controls. Synovial fluid [SF] samples were taken from all RA and OA for measuring HGF with ELISA technique. Immunohistochemical staining of RAST revealed that HGFA and c-Met were strongly expressed infibroblasts, macrophages, endothelial cells and less so on synovial lining cells. But HGF was expressed faintly in macrophages andfibroblasts. While, in OAST, HGFA and c-Met were detected in the same cells as RAST but in a different distribution. HGF was localized in vascular endothelial cells. RT-PCR showed HGF, HGFA and c-Met mRNA in all RAST and all OAST. HGF levels in SF samples were higher in RA patients [range 5.6-39.2 ng/ml and mean 26.3 +/- 1.2 ng/ml] than OA controls [range 4.2-37.5 ng/ml and mean 11.2+2.4 ng/ml]. The differences were statistically significant [p<0.001]. A non-significant correlation was found between HGF-SF levels and disease activity score [DAS] [p>0.5]. HGFA, HGF and c-Met mRNA are expressed in ST in RA and OA. Lack of correlation between HGF-SF levels and DAS indicated that HGF played a regulatory role in the immunopathogenesis of RA