Zhang K, Zhang YQ, Ai WB, Hu QT, Zhang QJ, Wan LY, Wang XL, Liu CB, Wu JF. Hes1, an important gene for activation of hepatic stellate cells, is regulated by Notch1 and TGF-β/BMP signaling. World J Gastroenterol 2015; 21(3): 878-887 [PMID: 25624721 DOI: 10.3748/wjg.v21.i3.878]
Corresponding Author of This Article
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
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
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/
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 Processing time: 272 Days and 0 Hours
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.
