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  3. Notch signaling mediated by TGF-β/Smad pathway in concanavalin A-induced liver fibrosis in rats

Notch signaling mediated by TGF-β/Smad pathway in concanavalin A-induced liver fibrosis in rats

  • World J Gastroenterol. 2017 Apr 7;23(13):2330-2336. doi: 10.3748/wjg.v23.i13.2330.
Yi Wang 1,  Ruo-Wu Shen 1,  Bing Han 1,  Zhen Li 1,  Le Xiong 1,  Feng-Yu Zhang 1,  Bei-Bei Cong 1,  Bei Zhang 1
Affiliations

Affiliation

  • 1 Yi Wang, Zhen Li, Le Xiong, Feng-Yu Zhang, Bei-Bei Cong, Bei Zhang, Department of Immunology, Medical College of Qingdao University, Qingdao 266071, Shandong Province, China.
PMID: 28428712 DOI: 10.3748/wjg.v23.i13.2330
Abstract

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 mRNA 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 mRNA and protein expression of TGF-β signaling, such as TGF-β1 and SMAD3. TGF-β inhibitor also downregulated Notch1, Hes1 and Hes5, and mRNA 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.

Keywords

Concanavalin A; Liver fibrosis; Notch; Peripheral blood mononuclear cells; Transforming growth factor-β.

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