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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 28, 2016; 22(36): 8137-8148
Published online Sep 28, 2016. doi: 10.3748/wjg.v22.i36.8137
Regulation of the serotonin transporter in the pathogenesis of irritable bowel syndrome
Duo-Chen Jin, Hai-Long Cao, Meng-Que Xu, Si-Nan Wang, Yu-Ming Wang, Fang Yan, Bang-Mao Wang
Duo-Chen Jin, Hai-Long Cao, Meng-Que Xu, Si-Nan Wang, Yu-Ming Wang, Fang Yan, Bang-Mao Wang, Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin 300052, China
Hai-Long Cao, Fang Yan, Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 372320696, United States
Author contributions: Jin DC, Cao HL and Wang BM designed the review; Jin DC, Cao HL, Xu MQ, Wang SN and Wang YM collected and analyzed the literature; Jin DC and Cao HL wrote the paper; Jin DC, Cao HL, Xu MQ, Wang SN, Yan F and Wang BM modified the manuscript; all authors were involved in the final approval of the article.
Supported by the National Natural Science Foundation of China, No. 81300272, No. 81470796, No. 81570489 and No. 81570478, and the Tianjin Research Program of Application Foundation and Advanced Technology of China, No. 15JCZDJC36600.
Conflict-of-interest statement: The authors have no conflicts of interest.
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: Hai-Long Cao, MD, PhD, Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, 154 Anshan Road, Heping District, Tianjin 300052, China. cao_hailong@163.com
Telephone: +86-22-60362608 Fax: +86-22-27813550
Received: March 27, 2016
Peer-review started: March 28, 2016
First decision: May 12, 2016
Revised: May 28, 2016
Accepted: June 15, 2016
Article in press: June 15, 2016
Published online: September 28, 2016
Processing time: 182 Days and 17.6 Hours
Abstract

Serotonin (5-HT) and the serotonin transporter (SERT) have earned a tremendous amount of attention regarding the pathogenesis of irritable bowel syndrome (IBS). Considering that enteric 5-HT is responsible for the secretion, motility and perception of the bowel, the involvement of altered enteric 5-HT metabolism in the pathogenesis of IBS has been elucidated. Higher 5-HT availability is commonly associated with depressed SERT mRNA in patients with IBS compared with healthy controls. The expression difference of SERT between IBS patients and healthy controls might suggest that SERT plays an essential role in IBS pathogenesis, and SERT was expected to be a novel therapeutic target for IBS. Progress in this area has begun to illuminate the complex regulatory mechanisms of SERT in the etiology of IBS. In this article, current insights regarding the regulation of SERT in IBS are provided, including aspects of SERT gene polymorphisms, microRNAs, immunity and inflammation, gut microbiota, growth factors, among others. Potential SERT-directed therapies for IBS are also described. The potential regulators of SERT are of clinical importance and are important for better understanding IBS pathophysiology and therapeutic strategies.

Keywords: Irritable bowel syndrome; Serotonin; Serotonin transporter; Regulation; Therapy

Core tip: The serotonin transporter (SERT) participates in metabolizing serotonin in the gut and plays a crucial role in the pathogenesis of irritable bowel syndrome (IBS). This review summarizes the relevant evidence on the factors that might regulate SERT, including SERT gene polymorphisms, microRNAs, immunity and inflammation, gut microbiota and growth factors. This review also reveals several potential treatments targeting SERT for IBS patients.