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 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). alpha-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.


CONCLUSIONS
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.
Second Department of Pathology, Nagasaki University School of Medicine, Japan.
M S
MS
Razzaque
T
T
Taguchi
D000199:Actins / Q000032:analysis; D000818:Animals; D003094:Collagen / Q000032:analysis; D003893:Desmin / Q000032:analysis; D004041:Dietary Fats / Q000009:adverse effects; D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000032:analysis / Q000187:drug effects / Q000502:physiology*; D006937:Hypercholesterolemia / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D007674:Kidney Diseases / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D007678:Kidney Glomerulus / Q000737:chemistry* / Q000166:cytology; D008264:Macrophages / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013194:Staining and Labeling / Q000379:methods; D014746:Vimentin / Q000032:analysis
D000199:Actins; D003893:Desmin; D004041:Dietary Fats; D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C494662:Serpinh1 protein, rat; D014746:Vimentin; D003094:Collagen