黏着斑激酶相关非激酶对肝星状细胞活化及迁移功能的影响

目的:探讨黏着斑激酶相关非激酶（FRNK）对肝星状细胞（HSCs）活化及迁移功能的影响。方法:2019年3—9月，收集贵州医科大学附属医院肝胆外科9例肝纤维化患者肝组织标本。人体肝组织分为健康对照组与纤维化组。C57BL/6实验小鼠分为野生型（WT）、FRNK基因敲除型（FRNK -/-）两组，以四氯化碳（...

Effects of FRNK on activation and migration of hepatic stellate cells

Objective To investigate the effect of focal adhesion kinase related non kinase(FRNK)on the activation and migration of hepatic stellate cells(HSCs).Methods Human liver tissue was divided into healthy control group and fibrosis group from March 2019 to September 2019 in Affiliated Hospital of Guizhou Medical University.C57BL/6 mice were divided into wild type(WT)and FRNK gene knockout type(FRNK-/-)groups.The liver fibrosis model was established with carbon tetrachloride(CCl4).After that,FRNK gene overexpression(Ad-FRNK)was constructed with adenovirus vector.HE and Masson staining were used to evaluate the pathological changes and fiber deposition of liver tissue.Western blot was used to detect the expression of PY397-FAK andα-SMA protein.Mouse primary HSCs were extracted,and the effect of FRNK on HSCs migration was detected by wound healing,activation of Rac and Rho was detected by Western blot.Results The expression of PY397-FAK protein in human liver tissue with hepatic fibrosis was significantly higher than that in healthy control group(0.88±0.09 vs.0.73±0.09).FRNK was significantly lower than that in control group(0.68±0.09 vs.0.79±0.11).After animal model was set up,the degree of liver fibrosis in FRNK-/-mice(153±13)%was more serious than that in WT(100%)group.The expression of PY397-FAK andα-SMA protein was significantly elevated(2.50±0.23 vs.0.75±0.09,1.46±0.20 vs.0.92±0.10).After FRNK gene was re-expressed(100%),the degree of liver fibrosis was mainly reversed[(74±6)%],and the expression of PY397-FAK andα-SMA was accordingly decreased(0.68±0.11 vs.1.12±0.19,0.68±0.10 vs.0.85±0.06).In vitro,FRNK inhibited the migration of HSCs[WT∶FRNK-/-∶Ad-FRNK,(339±49)%∶(580±53)%∶(259±33)%]and the activation of Rac and Rho proteins(Rac:0.54±0.07 vs.0.91±0.10 vs.0.77±0.12,Rho:0.45±0.05 vs.0.64±0.06 vs.0.53±0.07),all P<0.01.Conclusions FRNK can inhibit the activation and migration of HSCs which contributed to liver fibrosis.The potential mechanism is related to down regulation of PY397-FAK and inhibition of Rac and Rho activation.