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

Background. Heat shock protein 47 (hsp47) is a collagen-specific stress pro tein and is shown to be involved in the synthesis/assembly of various colla gens 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 matr ix. Methods. Dietary-induced hypercholesterolemia was induced in male Wistar ra ts by giving 2% cholesterol diet for four months. Immunohistochemistry was used for localization of protein products for collagens (types I, III, and IV), alpha-smooth muscle actin, vimentin, desmin, and ED-1, a macrophage/mo nocyte 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 immunosta ining, desmin-positive glomerular epithelial cells were found to be the mai n 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 ro le in the excessive assembly/synthesis of collagens and could thereby contr ibute to the glomerulosclerosis found in dietary-induced hypercholesterolem ic rat kidneys.