Takagi T, Naito Y, Uchiyama K, Okuda T, Mizushima K, Suzuki T, Handa O, Ishikawa T, Yagi N, Kokura S, Ichikawa H, Yoshikawa T. Rebamipide promotes healing of colonic ulceration through enhanced epithelial restitution. World J Gastroenterol 2011; 17(33): 3802-3809 [PMID: 21987622 DOI: 10.3748/wjg.v17.i33.3802]
Corresponding Author of This Article
Yuji Naito, MD, PhD, Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, 602-8566 Kyoto, Japan. ynaito@koto.kpu-m.ac.jp
Article-Type of This Article
Original Article
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Tomohisa Takagi, Yuji Naito, Kazuhiko Uchiyama, Toshimitsu Okuda, Katsura Mizushima, Takahiro Suzuki, Osamu Handa, Takeshi Ishikawa, Nobuaki Yagi, Satoshi Kokura, Hiroshi Ichikawa, Toshikazu Yoshikawa, Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 602-8566 Kyoto, Japan
Author contributions: Takagi T and Naito Y conceived the experiments; Okuda T, Suzuki T and Ishikawa T performed the majority of in vivo experiments; Uchiyama K and Hand O performed the majority of in vitro experiments; Mizushima K, Yagi N and Kokura S performed molecular biological analysis; Takagi T, Ichikawa H and Yoshikawa T analyzed the data and were also involved in editing the manuscript. All authors discussed the results and commented on the manuscript.
Supported by A Grant-in-Aid for Scientific Research (B) to Toshikazu Yoshikawa (Grant No. 21390184) and Challenging Exploratory Research to Yuji Naito (No. 08101559) from the Japan Society for the Promotion of Science; A City Area Program to Toshikazu Yoshikawa and Yuji Naito from Ministry of Education, Culture, Sports, Science and Technology, Japan; An Adaptable and Seamless Technology Transfer Program through target-driven R&D to Yuji Naito from Japan Science and Technology Agency
Correspondence to: Yuji Naito, MD, PhD, Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, 602-8566 Kyoto, Japan. ynaito@koto.kpu-m.ac.jp
Telephone: +81-75-2515508 Fax: +81-75-2510710
Received: December 2, 2010 Revised: January 18, 2011 Accepted: January 25, 2011 Published online: September 7, 2011
Abstract
AIM: To investigate the efficacy of rebamipide in a rat model of colitis and restitution of intestinal epithelial cells in vitro.
METHODS: Acute colitis was induced with trinitrobenzene sulfonic acid (TNBS) in male Wistar rats. Rats received intrarectal rebamipide treatment daily starting on day 7 and were sacrificed on day 14 after TNBS administration. The distal colon was removed to evaluate the various parameters of inflammation. Moreover, wound healing assays were used to determine the enhanced restitution of rat intestinal epithelial (RIE) cells treated with rebamipide.
RESULTS: Intracolonic administration of rebamipide accelerated TNBS-induced ulcer healing. Increases in the wet weight of the colon after TNBS administration were significantly inhibited by rebamipide. The wound assay revealed that rebamipide enhanced the migration of RIE cells through phosphorylation of extracellular signal-regulated kinase (ERK) and activation of Rho kinase.
CONCLUSION: Rebamipide enema healed intestinal injury by enhancing restitution of RIE cells, via ERK activation. Rebamipide might be a novel therapeutic approach for inflammatory bowel disease.
