胃粘膜特异性分子GDDR的胃粘膜保护作用及分子机制研究

We have firstly cloned the novel gene GDDR, and we previously found that it was speciafically expressed in gastric epithelium. However, the functions of GDDR in gastric mucosa have not been studied. GDDR could interact with TFF1 and TFF2, both of which are classic gastric mucosa protection molecules and both speciafically expressed in gastric epithelium. We hypothesised that GDDR played an important role in gastric mucosa protection. By using the GDDR knock-out and transgenic mouse (specially expressed in gastric mucosa), the priliminary results showed that lacking GDDR could exacerbate the injury of gastric mucosa, and recombinant GDDR protein could alleviate the gastric mucosa injury of GDDR knockout mice. We also showed that GDDR could up-regulate PGE2,which is a classic molecule of gastric mucosal protection. This study will use animal models combined with cellular experiments to illustrate the detailed functions and mechnisms of GDDR in gastric mucosa protection. This study has significant merit for uncovering the mechnism of gastric mucosa protection and for improving the level of diagnosis and treatment for the gastric mucosa related diseases.

GDDR是申请人率先发现并克隆的新基因，特异表达于胃粘膜表层上皮细胞，可与TFF1、TFF2分子相互作用。TFF1、TFF2分子可通过多种途径发挥胃粘膜保护作用。由此我们推测GDDR在胃粘膜损伤和保护中可能发挥了重要的作用。GDDR的表达受到炎性因子的调控，幽门螺旋杆菌感染时其表达明显下调，而国内外尚无GDDR与胃粘膜保护相关的报道。我们利用GDDR基因敲除、转基因小鼠进行急性胃粘膜损伤实验发现基因敲除小鼠的胃粘膜损伤最严重，经GDDR重组蛋白预处理的胃损伤明显减轻，初步证实了GDDR的胃粘膜保护作用。我们前期也发现GDDR可促进胃粘膜保护分子PGE2的表达。本项目拟利用GDDR基因敲除和转基因小鼠急慢性胃损伤模型结合细胞学实验，进一步明确GDDR在胃粘膜损伤过程中的保护作用及其分子机制。该研究对发现新的胃粘膜保护分子机制，提高胃粘膜损伤相关疾病的诊治水平具有重要意义。

GDDR是本课题组率先发现并克隆的新基因，特异表达于胃粘膜表层上皮细胞， 可与 TFF1、TFF2分子相互作用。TFF1、TFF2分子可通过多种途径维持胃黏膜的稳态。由此我们推测 GDDR在胃粘膜损伤和保护中可能发挥了重要的作用。GDDR的表达受到炎性因子的调控，幽门螺旋杆菌感染时其表达明显下调，而国内外尚无GDDR与胃粘膜损伤相关的报道。我们利用GDDR基因敲除进行急性胃粘膜损伤实验发现野生型小鼠的胃粘膜损伤最严重，经GDDR重组蛋白预处理的胃损伤明显减轻，初步证实了GDDR的胃粘膜损伤作用。本项目利用GDDR基因敲除和野生型小鼠急慢性胃损伤模型结合细胞学实验，进一步明确GDDR在胃粘膜损伤过程中的作用及其分子机制。该研究对发现新的胃粘膜损伤机制，提高胃粘膜损伤相关疾病的诊治水平具有重要意义。