Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajiicho Hirokoji Kawaramachi Kamigyo-ku, Kyoto 602-8566, Japan.
Biochem Biophys Res Commun. 2010 Jan 1;391(1):1122-6. doi: 10.1016/j.bbrc.2009.12.035. Epub 2009 Dec 11.
Carbon monoxide (CO) has been reported to ameliorate colonic inflammation and improve experimental colitis. It is well known that mucosal restitution is important to improve colitis as well as reduction of mucosal inflammation. However, it has not been clear whether CO effects to colonic mucosal restitution or not. In general, colonic myofibroblast (MF) has been reported to play an important role of colonic epithelial cell restitution via constitutive secretion of TGF-beta. In this study, we showed CO (supplied by CO-releasing molecule; CORM) treated MF conditioned medium enhanced colonic epithelial cell (YAMC) restitution and we determined gene expression in colonic MF treated with CO using microRNA. The microRNA array suggested that miR-710 was significantly reduced in MF by CO treatment and the target gene of miR-710 is determined to fibroblast growth factor (FGF)15. The CO treated MF conditioned medium which FGF15 expression was silenced extinguished the enhancement effect of epithelial cell restitution. Our findings demonstrate that CO treatment to MF increased FGF15 expression via inhibition of miR-710 and FGF15 enhanced colonic epithelial cell restitution.
一氧化碳（CO）已被报道可改善结肠炎症并改善实验性结肠炎。众所周知，黏膜修复对于改善结肠炎以及减少黏膜炎症很重要。然而，目前尚不清楚 CO 是否对结肠黏膜修复有影响。一般来说，结肠肌成纤维细胞（MF）通过持续分泌 TGF-β，在结肠上皮细胞修复中发挥重要作用。在这项研究中，我们发现 CO（通过 CO 释放分子提供）处理的 MF 条件培养基增强了结肠上皮细胞（YAMC）的修复，并且我们使用 microRNA 确定了 CO 处理的结肠 MF 中的基因表达。microRNA 阵列表明，CO 处理可使 MF 中的 miR-710 显著减少，而 miR-710 的靶基因是成纤维细胞生长因子（FGF）15。沉默 FGF15 表达的 CO 处理 MF 条件培养基消除了增强上皮细胞修复的作用。我们的研究结果表明，CO 处理 MF 可通过抑制 miR-710 增加 FGF15 的表达，并且 FGF15 增强了结肠上皮细胞的修复。
