Yuan B, Tang WH, Lu LJ, Zhou Y, Zhu HY, Zhou YL, Zhang HH, Hu CY, Xu GY. TLR4 upregulates CBS expression through NF-κB activation in a rat model of irritable bowel syndrome with chronic visceral hypersensitivity. World J Gastroenterol 2015; 21(28): 8615-8628 [PMID: 26229403 DOI: 10.3748/wjg.v21.i28.8615]
Corresponding Author of This Article
Guang-Yin Xu, MD, PhD, Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Institute of Neuroscience, The Second Affiliated Hospital, Soochow University, 199 Ren-Ai Road, Suzhou 215123, Jiangsu Province, China. guangyinxu@suda.edu.cn
Research Domain of This Article
Neurosciences
Article-Type of This Article
Basic Study
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Yuan B, Tang WH, Lu LJ, Zhou Y, Zhu HY, Zhou YL, Zhang HH, Hu CY, Xu GY. TLR4 upregulates CBS expression through NF-κB activation in a rat model of irritable bowel syndrome with chronic visceral hypersensitivity. World J Gastroenterol 2015; 21(28): 8615-8628 [PMID: 26229403 DOI: 10.3748/wjg.v21.i28.8615]
Bo Yuan, Wei-Hong Tang, Yuan Zhou, Hong-Yan Zhu, You-Lang Zhou, Hong-Hong Zhang, Chuang-Ying Hu, Guang-Yin Xu, Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Institute of Neuroscience, The Second Affiliated Hospital, Soochow University, Suzhou 215123, Jiangsu Province, China
Li-Juan Lu, Department of Pain Management, Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China
Author contributions: Yuan B performed experiments, analyzed data, and prepared figures and the manuscript; Tang WH performed experiments, analyzed data and prepared figures; Lu LJ analyzed data, prepared figures and the manuscript; Zhou Y performed experiments and analyzed data; Zhu HY performed experiments and analyzed data; Zhou YL performed experiments; Zhang HH performed experiments and analyzed data; Hu CY analyzed data and prepared the manuscript; Xu GY designed experiments, prepared figures and edited the manuscript; Yuan B, Tang WH and Lu LJ contributed equally to this work.
Supported by National Natural Science Foundation of China, No. 81230024, No. 81471137 (to GYX) and No. 31400947 (to HHZ); and Priority Academic Program Development of Jiangsu Higher Education Institutions.
Institutional review board statement: The study was reviewed and approved by Soochow University Institutional Review Board.
Institutional animal care and use committee statement: Animal care and handling of the animals were approved by the Institutional Animal Care and Use Committee at Soochow University and were in strict accordance with the guidelines of the International Association for the Study of Pain.
Conflict-of-interest statement: All authors have no conflict of interest related to the manuscript.
Data sharing statement: Technical appendix, statistical code, and dataset were available from the corresponding author. Participants gave informed consent for data sharing. No additional data are available.
Correspondence to: Guang-Yin Xu, MD, PhD, Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Institute of Neuroscience, The Second Affiliated Hospital, Soochow University, 199 Ren-Ai Road, Suzhou 215123, Jiangsu Province, China. guangyinxu@suda.edu.cn
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Received: February 9, 2015 Peer-review started: February 10, 2015 First decision: March 10, 2015 Revised: April 3, 2015 Accepted: May 20, 2015 Article in press: May 21, 2015 Published online: July 28, 2015 Processing time: 170 Days and 17.7 Hours
Core Tip
Core tip: This study investigated the roles of toll-like receptor 4 (TLR4) and its signaling pathway in the pathogenesis of visceral hypersensitivity in a rat model of irritable bowel syndrome (IBS). We demonstrated that activation of TLR4 upregulates the expression of the endogenous hydrogen sulfide-synthesizing enzyme cystathionine β synthetase. This upregulation was mediated by enhanced translocation of nuclear factor-κB in dorsal root ganglion cells, through which it contributed to the visceral hypersensitivity in IBS-like rats. Our results suggest TLR4 plays a major role in the development of functional visceral pain and hence suggest a novel mechanism and potential therapeutic target for the treatment of chronic visceral pain in patients with IBS.
