AIM To explore the exact interaction between Notch and transforming growth factor(TGF)-β signaling in liver fibrosis. METHODS We established a rat model of liver fibrosis induced by concanavalin A. Peripheral blood m...AIM To explore the exact interaction between Notch and transforming growth factor(TGF)-β signaling in liver fibrosis. METHODS We established a rat model of liver fibrosis induced by concanavalin A. Peripheral blood mononuclear cells(PBMCs) were isolated from the modeled rats, and cultured with γ-secretase inhibitor DAPT and TGF-β inhibitor for 24 h. The m RNA levels of Notch and TGF-β signaling were detected by quantitative real-time polymerase chain reaction. Expression of Notch and TGF-β proteins was analyzed by western blotting.RESULTS Compared to control rats, Notch and TGF-β signaling was activated in PBMCs of model rats. Administration of DAPT and TGF-β inhibitor suppressed Notch and TGF-β signal transducer in PBMCs of model rats. DAPT reduced m RNA and protein expression of TGF-β signaling, such as TGF-β1 and Smad3. TGF-β inhibitor also downregulated Notch1, Hes1 and Hes5, and m RNA and protein expression of the Notch signaling pathway.CONCLUSION Notch and TGF-β signaling play a role in liver fibrosis. TGF-β signaling upregulates Notch signaling, which promotes TGF-β signaling.展开更多
基金Supported by the Natural Science Foundation of Shandong Province,No.2014ZRB01466
文摘AIM To explore the exact interaction between Notch and transforming growth factor(TGF)-β signaling in liver fibrosis. METHODS We established a rat model of liver fibrosis induced by concanavalin A. Peripheral blood mononuclear cells(PBMCs) were isolated from the modeled rats, and cultured with γ-secretase inhibitor DAPT and TGF-β inhibitor for 24 h. The m RNA levels of Notch and TGF-β signaling were detected by quantitative real-time polymerase chain reaction. Expression of Notch and TGF-β proteins was analyzed by western blotting.RESULTS Compared to control rats, Notch and TGF-β signaling was activated in PBMCs of model rats. Administration of DAPT and TGF-β inhibitor suppressed Notch and TGF-β signal transducer in PBMCs of model rats. DAPT reduced m RNA and protein expression of TGF-β signaling, such as TGF-β1 and Smad3. TGF-β inhibitor also downregulated Notch1, Hes1 and Hes5, and m RNA and protein expression of the Notch signaling pathway.CONCLUSION Notch and TGF-β signaling play a role in liver fibrosis. TGF-β signaling upregulates Notch signaling, which promotes TGF-β signaling.
