Collagen-binding Heat Shock Protein (HSP) 47 Expression in Anti-thymocyte Serum (ATS)-induced Glomerulonephritis

An increased accumulation of extracellular matrix (ECM), predominantly collagens, is the main component of the expanded mesangial matrix in anti-thymocyte serum (ATS)-induced glomerulonephritis (GN). Heat shock protein (HSP) 47 is a collagen-binding stress protein and has been shown to have a specific role in the intracellular processing of procollagen molecules. It is a collagen-specific molecular chaperone in various organs, but its role in the kidney in relation to matrix expansion is not yet known. This study was designed to assess whether increased ECM accumulation in ATS-induced GN is associated with HSP47. The expression of type I, type III and type IV collagens, with their molecular chaperone HSP47, was investigated in ATS-induced GN rat kidneys. Fifteen male Wistar rats were divided into two groups: ATS-induced GN rats (group I) and age-matched controls (group II). GN was induced by injecting a single dose of ATS (0.8 ml/100 g body weight). All the rats were killed on the third and tenth day of the experiment. In group I, 3 days after ATS injection, histological examination revealed a reduction in glomerular cell number with mesangiolysis. However, 10 days after ATS injection, histologically severe mesangial cell proliferation with expansion of the mesangial matrix was noted in group I rats. By semiquantitative analysis, compared with controls, increased type I, type III, and type IV collagen immunostaining was observed in the expanded mesangial matrix in ATS-induced GN (group I) rats on day 10. Immunoreactive HSP47 expression was weak in the intraglomerular cells and was occasionally seen in the interstitial cells in control kidneys. In contrast, strong immunostaining for HSP47 was noted in the glomeruli of the ATS-treated rat kidneys on day 10. In this study, there was a parallel increase of various collagens and their molecular chaperone HSP47 in the ATS-treated rat kidneys. Compared with controls, no significant difference in HSP47 expression was found in the ATS-treated rat kidneys without mesangial matrix expansion (3 days after ATS injection). It is concluded that overexpression of HSP47 might play a significant role in the excessive assembly of collagens and could subsequently contribute to the expansion of mesangial matrix found in ATS-treated rat kidneys.