Effect of angiotensin II on Rho-Rock pathway in rat hepatic stellate cell contraction / 南方医科大学学报

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the mechanisms of angiotonin II (AngII)-induced Ca(2+)-independent pathways mediated by Rho kinase in hepatic stellate cells (HSCs).</p><p><b>METHODS</b>HSC-T6 cells were treated with 1 micromol/L of AngII, and the subsequent cell contraction was directly observed with silicone rubber membrane culture method. The cells with 10 micromol/L AngII treatment were examined for myosin light chain (MLC) phosphorylation level using Western blotting, and the effects of irbesartan (a specific inhibitor of AngII 1- receptor) and Y27632 (a Rho kinase inhibitor) on AngII-induced MLC phosphorylation were evaluated. RT-PCR was used to detect the expression of Rock2 in Ca(2+)- independent pathways mediated by Rho kinase.</p><p><b>RESULTS</b>AngII induced HSC contraction and time-dependent MLC phosphorylation changes, which peaked 15 min after the treatment followed by gradual reduction. Irbesartan or Y27632 treatment significantly lowered MLC phosphorylation level in AngII-induced cells (P<0.01). The mRNA expression of Rock2 increased significantly after AngII treatment (P<0.01), but decreased following subsequent irbesartan or Y27632 treatment.</p><p><b>CONCLUSION</b>AngII induces HSC contraction through Ca(2+)-independent pathways mediated by Rho kinase.</p>