COEXPRESSION OF THE COLLAGEN-BINDING STRESS PROTEIN HSP47 GENE AND THE ALPHA-1(I) AND ALPHA-1(III) COLLAGEN GENES IN CARBON TETRACHLORIDE-INDUCED RAT-LIVER FIBROSIS

COEXPRESSION OF THE COLLAGEN-BINDING STRESS PROTEIN HSP47 GENE AND THE ALPHA-1(I) AND ALPHA-1(III) COLLAGEN GENES IN CARBON TETRACHLORIDE-INDUCED RAT-LIVER FIBROSIS
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DOI:
10.1172/jci117617
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发表时间:
1994-12-01
影响因子:
15.9
通讯作者:
NAGATA, K
NAGATA, K
中科院分区:
医学1区
文献类型:
--
作者:
MASUDA, H;FUKUMOTO, M;NAGATA, K

文献摘要

被引文献

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HSP47是一种胶原结合应激蛋白,被认为是活细胞合成和分泌前胶原过程中的一种胶原特异性分子伴侣。在一些细胞系中,HSP47的合成与胶原的合成相关。我们检测了在四氯化碳(CCl4)诱导的大鼠肝纤维化过程中HSP47mRNA的表达。Northern印迹分析显示,肝纤维化过程中HSP47mRNA的表达与α1(I)和α1(III)胶原mRNAs平行表达。通过原位杂交,HSP47转录本的分布与α1(I)胶原相似,仅在胶原纤维内的细胞中观察到。经结蛋白免疫组织化学染色证实这些胶原阳性细胞为Ito细胞。单次给予CCl4的大鼠肝脏中未见高水平的HSP47mRNA表达,提示HSP47mRNA的诱导不是由于CCl4作为应激源的直接作用,而是由于肝纤维化的进展。本文还将对HSP47在肝纤维化中的作用进行讨论。
HSP47 is a collagen-binding stress protein and is assumed to act as a collagen-specific molecular chaperone during the biosynthesis and secretion of procollagen in the living cell. The synthesis of HSP47 has been reported to correlate with that of collagen in several cell lines.We examined the expression of HSP47 mRNA during the progression of carbon tetrachloride (CCl4)-induced liver fibrosis in rats. Northern blot analysis revealed that the expression of HSP47 mRNA was markedly induced during the progression of fibrosis in parallel with alpha 1(I) and alpha 1(III) collagen mRNAs. By in situ hybridization, the distribution of HSP47 transcripts was similar to that of alpha 1(I) collagen and was observed only in cells lining collagen fibrils. These collagen-positive cells were confirmed to be Ito cells by immunohistochemistry for desmin. The absence of high levels of HSP47 mRNA in the liver of rats treated with only a single administration of CCl4 indicated that the induction of HSP47 mRNA was not due to the direct effect of CCl4 as a stressor, but was due to the progression of liver fibrosis. The function of HSP47 in liver fibrosis will also be discussed.