Expression of heat-shock protein 47 in mouse liver

Abstract

Expression of heat-shock protein 47 in intact and fibrotic liver and in hepatic constituent cells was investigated in mice. Immunohistochemical study of intact liver and Western blot analysis of the protein from isolated liver cells revealed that stellate cells and smooth muscle cells of interlobular vessels, but not hepatocytes, Kupffer cells, or endothelial cells, expressed heat-shock protein 47. The protein was found in both vitamin-A-storing stellate cells and myofibroblast-like cells. The amount of the protein in cultured stellate cells was reduced by dexamethasone but was not regulated by quercetin, transforming growth factor beta, interferon gamma, or retinoic acid. In CCl4-treated or bile-duct-ligated mouse liver, the number of cells positive for heat-shock protein 47 markedly increased in the centrilobular area or around the periportal area, respectively, and the level of heat-shock protein 47 also increased.

Expression of HSP47, a collagen-specific chaperone, in normal and diseased human liver

“…A similar pattern of HSP47 immunoreactivity has previously been reported in normal chicken and mouse liver, which has been attributed to quiescent HSC. 11,15 We have also observed HSP47-positive sinusoidal lining cells in normal rat livers (data not shown). Our finding that HSP47 expression in normal human liver colocalizes with synaptophysin, an established marker of HSC, 17 confirms the identity of the HSP47-positive cells as stellate cells.…”

“…Although we did not compare HSP47 expression in quiescent and activated human HSC, levels of HSP47 in murine HSC have been reported to remain unaltered during activation in vitro. 11 These findings are particularly intriguing in view of that fact that the transcriptional regulation of HSP47 in BALB/c 3T3 cells involves the Kruppel-like factor KLF6 (Zf9). 28 In rat HSC, KLF6 is rapidly induced in response to liver injury and participates in the regulation of genes associated with the fibrogenic phenotype of HSC.…”

“…1 Although the precise role of HSP47 in the processing of procollagens has not been established, 2,3 expression of HSP47 is increased in fibrotic human lung, kidney and skin [4][5][6][7] and in animal models of lung, kidney and liver fibrosis. [8][9][10][11] Recent studies have suggested that levels of procollagen gene expression and rates of procollagen synthesis are regulated coordinately with HSP47. 12 In support of this concept, antisense oligonucleotides to HSP47 have been shown to reduce renal collagen accumulation in experimental glomerulonephritis and to inhibit scar formation in a cutaneous wounding model, suggesting that HSP47 plays a pivotal role in the pathogenesis of tissue fibrosis.…”

“…10 Similarly, immunoreactive HSP47 increased in the livers of mice treated with carbon tetrachloride or bile-duct ligation. 11 Despite the apparent importance of HSP47 in hepatic fibrogenesis, its expression in normal and diseased human liver has not been investigated previously. Accordingly, the aims of this study were to investigate the expression of HSP47 in human liver, its regulation in human HSC and the feasibility of modulating procollagen production by altering expression of HSP47 by human HSC.…”

Chronic Hepatotoxicity of Carbon Tetrachloride in HSP-70 Knock Out Mice

“…HSP25 is associated with increased resistance or tolerance to hepatotoxicants in the company of HSP70 [7]. Besides, HSP47, a collagen-binding stress protein, is assumed to act as a collagen-specific molecular chaperone during the biosynthesis and secretion of pro-collagen in the living cells [2]. In the liver of CCl 4 -treated or bile duct-ligated mice, the number of HSP47-positive cells markedly increased in the centrilobular or around the periportal area, showing an increased level of HSP47 [2].…”