肌成纤维细胞
病理
肝星状细胞
纤维化
胆管
原位杂交
增生
肝损伤
肝内胆管
胆汁淤积
细胞外基质
免疫组织化学
细胞角蛋白
医学
生物
内分泌学
内科学
基因表达
细胞生物学
生物化学
基因
作者
Grant A. Ramm,Sandra C. Carr,Kim R. Bridle,Lin Li,Robert S. Britton,Darrell H. G. Crawford,Carol Vogler,Bruce R. Bacon,Thomas F. Tracy
出处
期刊:Liver
[Wiley]
日期:2000-10-01
卷期号:20 (5): 387-396
被引量:38
标识
DOI:10.1034/j.1600-0676.2000.020005387.x
摘要
Myofibroblasts are the primary cells responsible for increased matrix deposition in hepatic fibrosis. Activation of hepatic stellate cells and portal fibroblasts to myofibroblasts during cholestatic liver injury is accompanied by increased expression of the activation marker, alpha-smooth muscle actin (SMA), and collagen genes. In contrast to our understanding of injury, the cellular mechanisms of liver repair are not well defined. This study was designed to examine the morphological relationship between bile duct hyperplasia, matrix deposition and myofibroblast phenotype in a model of chronic cholestatic liver injury and repair.Reversible extrahepatic obstruction was accomplished in rats using a soft vessel loop suspended from the anterior abdominal wall: duct manipulation alone was performed in sham-operated controls. After 7 days, rats were either sacrificed or decompressed by release of the loop and subsequently sacrificed 2-10 days after reversal. Liver sections were obtained for in situ hybridization for procollagen alpha1(I) mRNA, immunohistochemical staining for SMA and cytokeratin 19, and histochemical staining for reticulin.Cholestatic livers demonstrated bile duct hyperplasia, which reversed to normal within 10 days after decompression. Fibrosis was also substantially reduced during this period. SMA-positive myofibroblasts were abundant and localized to regions adjacent to proliferating ducts and excess matrix in the obstructed animals. Decompressed livers showed a dramatic time-dependent reduction in the number of SMA-positive cells and in the expression of procollagen I mRNA.Our results show that the disappearance of bile duct hyperplasia after biliary decompression is accompanied by a similarly rapid loss of SMA-positive myofibroblasts. Both cellular events may abrogate enhanced matrix synthesis and allow repair to occur.
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