Zhou X, Zhang Y, Zhang J, Zhu H, Zhou X, Du W, Zhang X, Chen Q
Department of Pathology, Shanghai Medical University, 138 Yi Xue Yuan Road, Shanghai 200032, China.
Chin Med J (Engl). 2000 Mar;113(3):272-6.
To investigate the role of fibronectin (FN) receptor alpha 5 beta 1 in liver fibrosis.
Northern blot analysis and immunohistochemical techniques were used to observe changes in the expression of FN and FN receptor alpha 5 beta 1 on hepatic stellate cells (HSCs) in vivo and in vitro of rat liver fibrosis induced by CCl4.
(1) alpha 5 beta 1 was mainly detected in the endothelia and some of the desmin(DM) positive cells of the sinusoids in normal rat liver. The expression of alpha 5 beta 1 of DM positive cells detected by immunohistochemistry reached its peak at the 10th week of the experiment. The changes in FN expression were similar to that of alpha 5 beta 1. (2) The expression of FN, alpha 5 and beta 1 mRNAs in the experimental group was remarkably increased especially at the 6th week, compared to that of normal liver specimens. The expression of the three mRNAs of HSCs in vitro isolated from the experimental group (6 weeks) was higher than those from normal liver. (3) The expression of FN, alpha 5 and beta 1 mRNAs increased in normal rat HSCs after treatment with transforming growth factor-beta 1 (TGF-beta 1) for 2 hours. After 4 hours of treatment, the expression of the three mRNAs fell to levels similar to the control group. Immunocytochemistry revealed that the expression of alpha 5 beta 1 of HSCs reached its peak after 4 hours of treatment with TGF-beta 1 and dropped to normal 2 hours later.
These data suggest that HSCs normally express FN receptor alpha 5 beta 1. The activation of HSCs during liver fibrogenesis leads to an increase of FN, alpha 5 and beta 1 mRNA expression. The expression of FN and alpha 5 beta 1 of HSCs in vitro is up-regulated by TFG-alpha 5 beta 1. The detection of gene transcription of FN and its receptor by Northern blot analysis suggests the activation and proliferation of HSCs and thereby provides a sensitive signal of liver fibrosis.
研究纤连蛋白（FN）受体α5β1在肝纤维化中的作用。
采用Northern印迹分析和免疫组化技术，观察四氯化碳诱导的大鼠肝纤维化体内外模型中肝星状细胞（HSCs）上FN及FN受体α5β1表达的变化。
（1）正常大鼠肝脏中，α5β1主要在肝血窦内皮及部分结蛋白（DM）阳性细胞中检测到。免疫组化检测DM阳性细胞中α5β1的表达在实验第10周达到峰值。FN表达的变化与α5β1相似。（2）与正常肝脏标本相比，实验组中FN、α5和β1 mRNA的表达显著增加，尤其是在第6周。从实验组（6周）分离的体外培养的HSCs中这三种mRNA的表达高于正常肝脏来源的HSCs。（3）用转化生长因子-β1（TGF-β1）处理正常大鼠HSCs 2小时后，FN、α5和β1 mRNA的表达增加。处理4小时后，这三种mRNA的表达降至与对照组相似的水平。免疫细胞化学显示，用TGF-β1处理HSCs 4小时后α5β1的表达达到峰值，2小时后降至正常水平。
这些数据表明HSCs正常表达FN受体α5β1。肝纤维化形成过程中HSCs的激活导致FN、α5和β1 mRNA表达增加。体外培养的HSCs中FN和α5β1的表达受TFG-α5β1上调。通过Northern印迹分析检测FN及其受体的基因转录提示HSCs的激活和增殖，从而为肝纤维化提供一个敏感信号。
