Lu ZJ, Wu JJ, Jiang WL, Xiao JH, Tao KZ, Ma L, Zheng P, Wan R, Wang XP. MicroRNA-155 promotes the pathogenesis of experimental colitis by repressing SHIP-1 expression. World J Gastroenterol 2017; 23(6): 976-985 [PMID: 28246471 DOI: 10.3748/wjg.v23.i6.976]
Corresponding Author of This Article
Xing-Peng Wang, MD, PhD, Professor, Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No 100, Haining Road, Shanghai 200080, China. richardwxp@163.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/
World J Gastroenterol. Feb 14, 2017; 23(6): 976-985 Published online Feb 14, 2017. doi: 10.3748/wjg.v23.i6.976
MicroRNA-155 promotes the pathogenesis of experimental colitis by repressing SHIP-1 expression
Zhan-Jun Lu, Jian-Jiong Wu, Wei-Liang Jiang, Jun-Hua Xiao, Kai-Zhong Tao, Lei Ma, Ping Zheng, Rong Wan, Xing-Peng Wang
Zhan-Jun Lu, Jian-Jiong Wu, Wei-Liang Jiang, Kai-Zhong Tao, Lei Ma, Rong Wan, Xing-Peng Wang, Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
Jun-Hua Xiao, Ping Zheng, Department of Gastroenterology, Shanghai East Hospital, School of Medicine, Tong Ji University, Shanghai 200092, China
Author contributions: Lu ZJ and Wu JJ contributed equally to this study; Lu ZJ and Wu JJ performed the majority of experiments; Wang XP designed and supervised this research; Jiang WL and Xiao JH were responsible for part of molecular studies in vitro; while Tao KZ and Ma L conducted the establishment of animal models and treatment; Zheng P and Wan R did the data process and analyzation; Lu ZJ and Wu JJ wrote this paper.
Institutional review board statement: This study (2015KY154) was approved by the Institutional Review Board of Shanghai First People’s Hospital Affiliated to Nanjing Medical University.
Institutional animal care and use committee statement: All protocols concerning laboratory animal usage in this study (2015KY154) were validated by the Animal Care Ethics Committee of Shanghai First People’s Hospital.
Conflict-of-interest statement: The authors declare no conflict of interest.
Data sharing statement: Technical appendix, statistical code, and dataset are available from the corresponding author at richardwxp@163.com.
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: Xing-Peng Wang, MD, PhD, Professor, Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No 100, Haining Road, Shanghai 200080, China. richardwxp@163.com
Telephone: +86-21-63240090 Fax: +86-21-63241377
Received: June 29, 2016 Peer-review started: July 1, 2016 First decision: August 19, 2016 Revised: November 27, 2016 Accepted: December 16, 2016 Article in press: December 19, 2016 Published online: February 14, 2017 Processing time: 227 Days and 22.3 Hours
Abstract
AIM
To explore the mechanism by which microRNA-155 (miR-155) regulates the pathogenesis of experimental colitis.
METHODS
A luciferase assay was performed to confirm the binding of miR-155 to the SHIP-1 3’-UTR. MiR-155 mimics, negative controls and SHIP-1 expression/knockdown vectors were established and then utilized in gain- and loss-of-function studies performed in raw264.7 cells and primary bone marrow-derived macrophages (BMDMs). Thereafter, dextran sulfate sodium (DSS)-induced colitis mouse model with or without antagomiR-155 treatment was established, and the levels of miR-155 and SHIP-1, as well as the pro-inflammatory capabilities, were measured by western blot, quantitative polymerase chain reaction, and immunohistochemistry.
RESULTS
MiR-155 directly bound to the 3’-UTR of SHIP-1 mRNA and induced a significant decrease in SHIP-1 expression in both raw264.7 cells and primary BMDMs. MiR-155 markedly promoted cell proliferation and pro-inflammatory secretions including IL-6, TNF-α, IL-1β, and IFN-γ, whereas these effects could be reversed by the restoration of SHIP-1 expression. In vivo studies showed that antagomiR-155 administration could alleviate DSS-induced intestinal inflammation in Balb/c mice. Moreover, significantly increased SHIP-1 expression, as well as decreased Akt activation and inflammatory response, were observed in the antagomiR-155-treated mice.
CONCLUSION
MiR-155 promotes experimental colitis by repressing SHIP-1 expression. Thus, the inhibition of miR-155 might be a promising strategy for therapy.
Core tip: Our present study identifies SHIP-1 as the functional target of microRNA-155 (miR-155) in macrophages. The up-regulation of miR-155 during colitis led to a significant decrease in SHIP-1 expression as well as a marked enhancement in cell proliferation and pro-inflammatory secretions, whereas the restoration of SHIP-1 expression partly reversed these changes. We further confirmed that antagomiR-155 treatment effectively alleviates dextran sulfate sodium-induced intestinal inflammation in mice, correlated with a significant elevation in SHIP-1 expression levels. Our findings indicate a novel mechanism by which miR-155 influences colitis progression.
