Research on the treatment of inflammatory bowel diseases using Reg gene modified mice

Reg蛋白是胰腺、肾脏和胃肠道粘膜中表达的生长因子。我们以前发现Reg蛋白刺激胃肠道上皮细胞的生长。没有关于Reg蛋白对胃肠道粘膜的体内影响的数据。作为体内模型，我们采用了具有CMV启动子和具有PS2启动子的Reg-transgenic小鼠。我们还采用了Reg敲除小鼠。通过对Reg转基因小鼠的研究，我们发现Reg蛋白对胃上皮细胞的增殖和胃底腺的分化具有重要作用。此外，Reg蛋白在胃粘膜损伤后的胃上皮修复中也发挥着重要作用。通过对Reg-关节炎小鼠肠绒毛的研究，我们发现Reg蛋白在肠绒毛的发育和维持中起重要作用。将重组Reg蛋白经肛门给药于实验性结肠炎模型动物，发现Reg蛋白可促进肠上皮细胞增殖，加速实验性损伤的修复，提示Reg蛋白对炎症性肠病可能具有治疗作用。

Reg protein is a growth factor expressed in pancreas, kidney, and in gastrointestinal mucosa. We have previonoly found that Reg protein stimulates the growth of gastrointestinal epithelium. There was no data available concerning the in vivo effect of Reg protein on the gastrointestinal mucosa. As in vivo models, we have employed Reg-transgenic mice with CMV promoter and with PS2 promoter. We also employed Reg knockout mice. From the studies using Reg-transgenic mice, we have found that Reg protein is important for the proliferation of gastric epithelium and for the differentiation to gastric fundic glands. In addition, Reg protein was found to have pivotal role in the gastric epithelial repair from gastric mucosal injury. From the avolysis of reg-knuckout mice, we have found that Reg protein is important for the development and maintenance of intestinal villi. When recombinant Reg protein was trans-anally administered to model animals with experimental colitis, Reg protein was found to augment the proliferation of intestinal epithelium and accelerate the repairment of experimentally-induced epithelial damage.All of these results suggested the possible therapeutic effect of Reg protein for the inflammatory bowel diseases.