Increased Expression of Collagen-binding Heat Shock Protein 47 in Human and Experimentally-induced Rat Crescentic Glomerulonephritis: its Possible Role in Fibrotic Process

The 47-kD heat shock protein 47 (HSP47), a major collagen-binding stress protein, is thought to play an important role in fibrotic diseases. To investigate the role of HSP47 in the fibrotic process of crescent formation in renal glomeruli, involvement of HSP47 was examined in both human and experimental crescentic glomerulonephritis (GN). Renal biopsy sections of 15 cases of crescentic GN and 5 cases of minimal change nephrotic syndrome were examined for the expression of HSP47. Experimental crescentic GN was induced by anti-glomerular basement membrane antibody in rats. HSP47 expression was examined in crescents at various stages of formation (days 7, 14, 21, 28 and 42). In human renal biopsy sections, increased expression of HSP47 was noted in the cellular stage of crescent formation. Double immunostaining demonstrated that the majority of ﾎｱ-smooth muscle actin-positive cells in the crescent expressed HSP47. However, its expression was less in fibrous crescents, which were predominantly composed of type III collagen. In the rat model of crescent GN, increased expression of HSP47, both at mRNA and protein levels, was noted in the early stages of cellular crescents. However, its expression was decreased in the late stages of fibrous crescents. Based on the collagen synthesis ability of HSP47, we speculate that overexpression of HSP47 in cellular crescents may contribute to the excessive synthesis/ assembly of collagens and subsequently lead to irreversible fibrous crescent formation