EXTRACELLULAR-MATRIX GENE-EXPRESSION INCREASES PREFERENTIALLY IN RAT LIPOCYTES AND SINUSOIDAL ENDOTHELIAL-CELLS DURING HEPATIC-FIBROSIS INVIVO
EXTRACELLULAR-MATRIX GENE-EXPRESSION INCREASES PREFERENTIALLY IN RAT LIPOCYTES AND SINUSOIDAL ENDOTHELIAL-CELLS DURING HEPATIC-FIBROSIS INVIVO
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DOI：
10.1172/jci114886
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发表时间：
1990-11-01
影响因子：
15.9
通讯作者：
MCGUIRE, RF
中科院分区：
文献类型：
--
作者：
MAHER, JJ;MCGUIRE, RF
肝实质或非实质肝细胞是否在肝纤维化的病理生理中起主导作用，目前还没有明确的证据。我们通过定量分析来自正常和纤维化大鼠肝脏的纯化肝细胞、窦状内皮细胞和脂肪细胞中I、III、IV型胶原蛋白和层粘胶蛋白的特异性mrna的相对丰度来解决这个问题。在正常肝脏中，I型胶原基因在所有细胞类型中表达最少；III型和IV型胶原mRNA在内皮细胞和脂肪细胞中可见，而在肝细胞中不可见。所有细胞类型中均存在层粘连蛋白mRNA。胆管结扎或四氯化碳诱导的纤维形成与非实质细胞中I型和III型胶原mRNA的显著增加有关。与正常脂肪细胞相比，来自纤维化动物的脂肪细胞显示出I型胶原mRNA的>增加了30倍，>相对于肝细胞增加了40倍。III型胶原mRNA是正常脂肪细胞的5倍，是肝细胞的120倍。内皮细胞表现出I型胶原mRNA的孤立增加，达到正常肝脏的5倍。在纤维形成过程中，非实质细胞中IV型胶原蛋白和层粘连蛋白基因表达不明显增加；事实上，内皮细胞中IV型胶原和层粘连蛋白的mRNA减少了50%。尽管在纤维形成过程中，非实质细胞的基质基因表达发生了明显的变化，但在肝细胞中没有发现变化。我们得出结论，非实质肝细胞，特别是脂肪细胞，是体内肝纤维化的重要效应器。
Whether parenchymal or nonparenchymal liver cells play a predominant role in the pathophysiology of hepatic fibrosis has not been firmly established in vino. We have addressed this question by quantitating the relative abundance of specific mRNAs for collagen types I, III, and IV, and laminin in purified populations of hepatocytes, sinusoidal endothelial cells, and lipocytes from normal and fibrotic rat liver. In normal liver, type I collagen gene expression was minimal in all cell types; mRNA for types III and IV collagen were apparent in endothelial cells and lipocytes, but not in hepatocytes. Laminin mRNA was present in all cell types. Induction of fibrogenesis by either bile duct ligation or carbon tetrachloride administration was associated with a substantial increase in mRNA for types I and III collagen in nonparenchymal cells. Lipocytes from fibrotic animals exhibited a > 30-fold increase in type I collagen mRNA relative to normal lipocytes, and > 40-fold relative to hepatocytes. Type III collagen mRNA reached 5 times that in normal lipocytes and > 120 times that in hepatocytes. Endothelial cells exhibited an isolated increase in type I collagen mRNA, reaching five times that in normal liver. Type IV collagen and laminin gene expression were not significantly increased in nonparenchymal cells during fibrogenesis; in fact, mRNA for type IV collagen and laminin decreased by up to 50% in endothelial cells. Despite the pronounced changes that occurred in matrix gene expression in nonparenchymal cells during fibrogenesis, no change was noted in hepatocytes. We conclude that nonparenchymal liver cells, particularly lipocytes, are important effectors of hepatic fibrosis in vivo.