Investigation of the possibility of Trefoil Factor Family as a therapeutics for post-EMR (endoscopic mucosal resection) gastric ulcer

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Intesitnal trefoil factor (ITF) plays an important role in the process of wound healing of gastrointestinal tract. Endoscopic mucosal resection (EMR) is a prevailing procedure for the treatment of early gastric cancers. Following the procedure, patients need limited diet or medication such as anti-acid or muco-protective drugs for the protection of denuded area or facilitating the healing of the artificial ulceration. We have investigated if ITF could be useful as the therapeutics for the artificial ulceration caused by endoscopic mucosal resection (EMR). The effect of ITF was tested in a rat stomach model of EMR. The level of ITF gene expression in rat stomach was almost undetectable. Increased endogenous expression of ITF was observed on 1 day after EMR and maximum level was observed on day 3, which was examined by RT-PCR. Although exogenous ITF sprayed upon ulcer surface stayed only up to postoperative day 1, ITF significantly accelerated the mucosal healing in macroscopically as we … More ll as microscopically. The characteristic appearances of ulcer healing treated by ITF were attenuated the extent or the degree of inflammation, reduced necrosis of epithelial cells adjacent to the ulcer, enhanced re-epithelization of ulcer surface and decreased fibrosis. In aggregate, ITF accelerated the healing of artificial ulceration in a manner similar to natural healing process of gastric ulcer. In the view point of safety of ITF as clinical therapeutics, the stimulatory effect of TFF3 on proliferative response was evaluated in either endogenous TFF3 positive or negative gastric cancer cell lines. ITF did not have any stimulatory effect on all cell lines tested, which suggesting that ITF might be a effective therapeutics for the ulcerations caused by EMR for the management of carcinomas. In summary, our present study demonstrated the clinical importance of restitution, which is an initial phase of epithelial wound healing and promoted by exogenous administration of ITF. ITF might be a new therapeutics against post-EMR gastric ulceration. Less