OBJECTIVE: To investigate the role of fibronectin (FN) receptor alpha 5 beta 1 in liver fibrosis. METHODS: 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. RESULTS: (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. CONCLUSION: 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.
OBJECTIVE: To investigate the role of fibronectin (FN) receptor alpha 5 beta 1 in liver fibrosis. METHODS: 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 ratliver fibrosis induced by CCl4. RESULTS: (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. CONCLUSION: 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.
Authors: N Uyama; L Zhao; E Van Rossen; Y Hirako; H Reynaert; D H Adams; Z Xue; Z Li; R Robson; M Pekny; A Geerts Journal: Gut Date: 2006-02-16 Impact factor: 23.059