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Chronic tissue injury with fibrosis results in the disruption of tissue architecture,organ dysfunction,and eventual organ failure.Therefore,the development of effective antifibrotic drugs is urgently required.IMB-S7 is novel biphenyl compound derived from bifendate (biphenyldicarboxylate) that is used for the treatment of chronic hepatitis in China.In the current study we investigated the potential of IMB-S7 as an antihepatic fibrosis agent.In bile duct ligation (BDL) rat model,oral administration of IMB-S7 (400 mg· kg-1· d-1,for 14 days) significantly ameliorated BDL-induced liver necrosis,bile duct proliferation,and collagen accumulation.We then showed that IMB-S7 treatment markedly suppressed the TGF-β/Smad pathway in human hepatic stellate cell line LX2 and mouse primary HSCs,as well as in liver samples of BDL rats,thus inhibiting the transcription of most fibrogenesisassociated genes,including TGF-β1,COL1A1,and ACTA2.Furthermore,IMB-S7 treatment significantly suppressed the expression of integrin αv at the mRNA and protein levels in TGF-β-treated LX2 cells and liver samples of BDL rats.Using integrin αv overexpression and silencing,we demonstrated that integrin αv activity correlated positively with the activation of TGF-β/Smad pathway.Based on dual luciferase assay and DNA affinity precipitation assay,we revealed that IMB-S7 inactivated integrin αv through competitively inhibiting the binding of Sp1,a transcription factor,to the integrin αv (ITGAV) promoter (-173/-163 bp).These results suggest that IMB-S7 inhibits HSCs activation and liver fibrosis through Sp1-integrin αv signaling,and IMB-S7 may be a promising candidate to combat hepatic fibrosis in the future.