Role of glomerular epithelial cell-derived heat shock protein 47 in experimental lipid nephropathy

Abstract

Background. Heat shock protein 47 (hsp47) is a collagen-specific stress protein and is shown to be involved in the synthesis/assembly of various collagens as a molecular chaperone. This study was undertaken to investigate the possible role of hsp47 in dietary-induced hypercholesterolemic rat kidneys, which showed glomerular hypercellularity with expansion of mesangial matrix. Methods. Dietary-induced hypercholesterolemia was induced in male Wistar rats by giving 2% cholesterol diet for four months. Immunohistochemistry was used for localization of protein products for collagens (types I, III, and IV), α-smooth muscle actin, vimentin, desmin, and ED-1, a macrophage/monocyte marker, and hsp47 in control and hypercholesterolemic rat kidneys. Results. Compared with the control, increased accumulation of collagens was accompanied with increased expression of hsp47 in hypercholesterolemic rat kidneys, with predominant expression in the glomeruli. By double immunostaining, desmin-positive glomerular epithelial cells were found to be the main source of hsp47 in hypercholesterolemic rat kidneys. Conclusion. From these results, it is concluded that induced expression of hsp47 by phenotypically altered glomerular epithelial cells might play a role in the excessive assembly/synthesis of collagens and could thereby contribute to the glomerulosclerosis found in dietary-induced hypercholesterolemic rat kidneys. © 1999 by the International Society of Nephrology.