Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 21, 2015; 21(3): 878-887
Published online Jan 21, 2015. doi: 10.3748/wjg.v21.i3.878
Hes1, an important gene for activation of hepatic stellate cells, is regulated by Notch1 and TGF-β/BMP signaling
Kai Zhang, Yan-Qiong Zhang, Wen-Bing Ai, Qing-Ting Hu, Qiao-Juan Zhang, Lin-Yan Wan, Xiao-Lian Wang, Chang-Bai Liu, Jiang-Feng Wu
Kai Zhang, Yan-Qiong Zhang, Qing-Ting Hu, Qiao-Juan Zhang, Lin-Yan Wan, Xiao-Lian Wang, Chang-Bai Liu, Jiang-Feng Wu, Medical College, China Three Gorges University, Yichang 443002, Hubei Province, China
Wen-Bing Ai, the Second College of Clinical Medical Science, China Three Gorges University, Yichang 443000, Hubei Province, China
Chang-Bai Liu, Jiang-Feng Wu, Institute of Molecular Biology, Medical College, China Three Gorges University, Yichang 443002, Hubei Province, China
Author contributions: Zhang K, Zhang YQ and Ai WB contributed equally to this work and wrote the manuscript; Hu QT, Zhang QJ, Wan LY and Wang XL give some help for this work; Wu JF and Liu CB guide the research; Wu JF and Liu CB revised and approved the article to be published.
Supported by National Natural Science Foundation of China, No. 81170412, No. 81070348 and No. 81200307; Health Department of Hubei Province of China, No. JX6C-26.
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: Jiang-Feng Wu, Professor, Institute of Molecular Biology, Medical College, China Three Gorges University, 8 Daxue Road, Xiling District, Yichang 443002, Hubei Province, China. 313229177@qq.com
Telephone: +86-717-6397328 Fax: +86-717-6397328
Received: April 23, 2014
Peer-review started: April 24, 2014
First decision: May 29, 2014
Revised: June 18, 2014
Accepted: July 15, 2014
Article in press: July 16, 2014
Published online: January 21, 2015
Core Tip

Core tip: In our paper, we found that Notch signaling appears to crosstalk with TGF-β/BMP signaling and co-regulates the expression of Hes1 in hepatic stellate cells. Notch1 may keep Hes1 protein in a reasonable range due to Hes1 auto-negative feedback, allowing Notch1 to repress the expression of α-SMA and collagen1α2 (COL1α2). Over-expression of Hes1 via transfection, thus lacking the negative feedback, enhances the promoter activities of α-smooth muscle actin (α-SMA) and COL1α2, consistent with the finding when Hes1 is captured by a Hes1-decoy oligodeoxynucleotide. This may provide an anti-fibrotic strategy against hepatic fibrosis. Further investigations in the future on the molecular mechanism by which Hes1 regulates the expression of α-SMA and COL1α2 should provide additional support for such an approach.