Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 7, 2017; 23(13): 2330-2336
Published online Apr 7, 2017. doi: 10.3748/wjg.v23.i13.2330
Notch signaling mediated by TGF-β/Smad pathway in concanavalin A-induced liver fibrosis in rats
Yi Wang, Ruo-Wu Shen, Bing Han, Zhen Li, Le Xiong, Feng-Yu Zhang, Bei-Bei Cong, Bei Zhang
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
Ruo-Wu Shen, Department of Anatomy, Medical College of Qingdao University, Qingdao 266071, Shandong Province, China
Bing Han, Department of Hepatobiliary Surgery, Affiliated Hospital of Qingdao University, Qingdao 266071, Shandong Province, China
Author contributions: Zhang B supervised the entire study; Wang Y and Shen RW contributed equally to this research and should be considered as co-first authors; Wang Y, Shen RW, Han B, Li Z, Xiong L, Zhang FY and Cong BB performed the research and analyzed the data; Wang Y wrote the paper; all authors have read and approved the final manuscript.
Supported by the Natural Science Foundation of Shandong Province, No. 2014ZRB01466.
Institutional review board statement: The study was reviewed and approved by the Qingdao University Medical College Institutional Review Board.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of Qingdao University Medical College (No. SCXK20090007).
Conflict-of-interest statement: We declare that there are no conflicts of interest to disclose.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Bei Zhang, Department of Immunology, Medical College of Qingdao University, 308 Ningxia Road, Qingdao 266071, Shandong Province, China. zhangbei124@aliyun.com
Telephone: +86-186-61980199
Received: December 22, 2016
Peer-review started: December 23, 2016
First decision: January 10, 2017
Revised: January 26, 2017
Accepted: February 17, 2017
Article in press: February 17, 2017
Published online: April 7, 2017
Processing time: 105 Days and 6.8 Hours
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: Notch; Peripheral blood mononuclear cells; Concanavalin A; Transforming growth factor-β; Liver fibrosis

Core tip: Notch and transforming growth factor (TGF)-β activation plays an important role in liver fibrosis induced by concanavalin A. It has been shown that TGF-β facilitates liver fibrosis. However, the mechanism of action of Notch in liver fibrosis is not fully understood. In this study, we found that excessive activation of TGF-β regulated Notch in liver fibrosis in rats, and that inhibition of TGF-β signaling blocked Notch signaling and vice versa. This may be a complementary mechanism of liver fibrosis, which provides a potential immunotherapeutic strategy.