Background Angiotensin Ⅱ （Ang Ⅱ） is a very important vasoactive peptide that acts upon hepatic stellate cells （HSCs）, which are major effector cells in hepatic cirrhosis and portal hypertension. The present stud...Background Angiotensin Ⅱ （Ang Ⅱ） is a very important vasoactive peptide that acts upon hepatic stellate cells （HSCs）, which are major effector cells in hepatic cirrhosis and portal hypertension. The present study was aimed to investigate the effects of Ang Ⅱ and angiotensin Ⅱ type 1 receptor antagonist （AT1RA） on the proliferation, contraction and collagen synthesis in HSCs.Methods HSC-T6 rat hepatic stellate cell line was studied. The proliferation of the HSC cells was evaluated by MTT colorimetric assay while HSC DNA synthesis was measured by ^3H-thymidine incorporation. The effects of angiotensin Ⅱ and AT1RA on HSCs contraction were studied by analysis of the contraction of the collagen lattice. Cell culture media were analyzed by RT-PCR to detect secretion of collagen Ⅰ （Col Ⅰ）, collagen Ⅲ （Col Ⅲ） and transforming growth factor β1 （TGF-β1） by enzyme linked immunosorbent assay. HSC was harvested to measure collagen Ⅰ, collagen Ⅲ and tissue inhibitor of metalloproteinase-1 （TIMP-1） mRNA expression.Results Ang Ⅱ （（1×10^-10-1×10^-4）mol/L）stimulated DNA synthesis and proliferation in HSCs compared with untreated control cells. AT1RA inhibited angiotensin Ⅱ induced proliferation of HSCs. A linear increase in the contractive area of collagen lattice correlated with the concentration of angiotensin Ⅱ （1×10^-9-1×10^-5 mol/L） and with time over 48 hours. AT1RA blocks angiotensin Ⅱ induced contraction of collagen lattice. Col Ⅰ, Col Ⅲ and TGF-β1 levels of the Ang Ⅱ group were higher than those of control group and this increase was downregulated by AT1RA. The mRNA expressions of Col Ⅰ, Col Ⅲ and TIMP-1 were higher in HSCs from the Ang Ⅱ group than the control group and downregulated by AT1RA. Conclusions Angiotensin Ⅱ increased DNA synthesis and proliferation of HSCs in a dose-dependent manner, stimulated the contraction of HSCs dose- and time-dependently. Angiotensin also promoted excretion of Col I, Col Ⅲ and TGF-β1 levels an展开更多
文摘Background Angiotensin Ⅱ （Ang Ⅱ） is a very important vasoactive peptide that acts upon hepatic stellate cells （HSCs）, which are major effector cells in hepatic cirrhosis and portal hypertension. The present study was aimed to investigate the effects of Ang Ⅱ and angiotensin Ⅱ type 1 receptor antagonist （AT1RA） on the proliferation, contraction and collagen synthesis in HSCs.Methods HSC-T6 rat hepatic stellate cell line was studied. The proliferation of the HSC cells was evaluated by MTT colorimetric assay while HSC DNA synthesis was measured by ^3H-thymidine incorporation. The effects of angiotensin Ⅱ and AT1RA on HSCs contraction were studied by analysis of the contraction of the collagen lattice. Cell culture media were analyzed by RT-PCR to detect secretion of collagen Ⅰ （Col Ⅰ）, collagen Ⅲ （Col Ⅲ） and transforming growth factor β1 （TGF-β1） by enzyme linked immunosorbent assay. HSC was harvested to measure collagen Ⅰ, collagen Ⅲ and tissue inhibitor of metalloproteinase-1 （TIMP-1） mRNA expression.Results Ang Ⅱ （（1×10^-10-1×10^-4）mol/L）stimulated DNA synthesis and proliferation in HSCs compared with untreated control cells. AT1RA inhibited angiotensin Ⅱ induced proliferation of HSCs. A linear increase in the contractive area of collagen lattice correlated with the concentration of angiotensin Ⅱ （1×10^-9-1×10^-5 mol/L） and with time over 48 hours. AT1RA blocks angiotensin Ⅱ induced contraction of collagen lattice. Col Ⅰ, Col Ⅲ and TGF-β1 levels of the Ang Ⅱ group were higher than those of control group and this increase was downregulated by AT1RA. The mRNA expressions of Col Ⅰ, Col Ⅲ and TIMP-1 were higher in HSCs from the Ang Ⅱ group than the control group and downregulated by AT1RA. Conclusions Angiotensin Ⅱ increased DNA synthesis and proliferation of HSCs in a dose-dependent manner, stimulated the contraction of HSCs dose- and time-dependently. Angiotensin also promoted excretion of Col I, Col Ⅲ and TGF-β1 levels an
