Expression of heat shock protein 47 is increased in remnant kidney and correlates with disease progression

Abstract

Glomerulosclerosis is characterized by accumulation of the mesangial extracellular matrix, including type I and V collagen. The processing for the collagens in the glomeruli may play a critical role for development of glomerulosclerosis. We examined the expression of heat shock protein 47 (HSP47), a collagen-binding molecular chaperone in the progressive glomerulosclerosis model. Subtotally nephrectomized rats, unlike sham-operated rats, developed focal and segmental glomerulosclerosis. Immunological staining demonstrated an increased expression of HSP47 which paralleled the expression of type I and IV collagen in the glomeruli of the nephrectomized rats as the glomerulosclerosis developed. The mRNA levels encoding type I and type IV collagen and HSP47 were increased 3.4 fold, 3.6 fold and 2.8 fold, respectively, at week 7 after nephrectomy. By in situ hybridization, the expression of HSP47 mRNA was determined to be localized to the glomeruli with segmental sclerosis. These results suggest that HSP47 may play a central role in the process of extracellular matrix accumulation during the development of glomerulosclerosis.

Advanced Glycation End Products Increase Collagen-specific Chaperone Protein in Mouse Diabetic Nephropathy

“…However, its role in kidney diseases in relation to sclerosis/ fibrosis in diabetic nephropathy and IgA nephropathy is completely unknown. We and others (8,28) have demonstrated that HSP47 in glomerulosclerosis is associated with collagen staining. Furthermore, the blocking of HSP47 with antisense oligonucleotides caused a dramatic amelioration of glomerular lesions in the rat glomerulonephritis model (9).…”

“…We recently reported that the expression of HSP47 was markedly increased in parallel with the development of glomerulosclerosis in a rat renal ablation model (8). We also found that the inhibition of HSP47 ameliorated glomerulosclerosis (9).…”

“…Thus, TGF-␤ is considered to be a mediator of collagen production in the models of fibrogenesis. Significant progress has recently been made in our understanding of the expression of the collagen genes and their transcriptional regulation by TGF-␤ (8,9). A recent report has shown that high glucose transiently induces a transcriptional activity of c-fos responsible for stimulation of the TGF-␤ (13).…”

The Kruppel-like Factor Zf9 and Proteins in the Sp1 Family Regulate the Expression of HSP47, a Collagen-specific Molecular Chaperone

“…The spatiotemporally concerted expression of HSP47 with collagens is also observed during mouse and chick embryonic development (10). In addition, a marked induction of HSP47 has been reported in the progression of fibrosis in various experimental fibrosis models, including liver cirrhosis (11), kidney fibrosis (12), and atherosclerosis (13). The down-regulation of hsp47 caused by introducing hsp47 antisense oligoribonucleotides into rat renal cells after the initiation of fibrosis markedly reduces the rate of the progression of fibrosis and reduces the levels of types I and III collagens in the kidney (14).…”

The Molecular Interactions of Heat Shock Protein 47 (Hsp47) and Their Implications for Collagen Biosynthesis

“…This early role must be significant. Increased Hsp47 expression has been linked to a number of diseases in which increased collagen deposition occurs, including arteriosclerosis (22,23), myocardial infarction (24), and hepatic (25), renal (26), and pulmonary fibrosis (27). Indeed Sunamoto et al (28) successfully reduced the progression of glomerulonephritis in a rat model by reducing Hsp47 expression.…”