慢性萎缩性胃炎（CAG）是一种重要的胃癌癌前病变，其发生的分子机制尚不完全清楚。我们在国内外首次报道了Slc26a9基因的缺失导致了胃癌的发生发展（Liu et al., FASEB 2015) 。我们进一步研究了Slc26a9基因与胃癌发生早期事件-CAG之间的关系：Slc26a9在CAG中表达明显下调，且在CAG发生至胃癌恶性进程中呈渐进性减弱。 Slc26a9基因的缺失导致小鼠发生CAG及恶性病理改变，并伴有P53、Shh、自噬信号通路的相关基因和蛋白质的改变。因此，我们推测：Slc26a9基因缺失或下调可能诱导P53、Shh、自噬等多种信号紊乱，致使胃粘膜上皮细胞的分化与稳态异常，从而导致CAG发生及恶性病理进展。本项目拟通过基因敲除小鼠模型和单细胞敲除模型的建立及人体临床样本收集，结合基因表达谱芯片、分子及细胞功能学实验等探寻Slc26a9在CAG发生发展的作用及主要调控机制。

Chronic atrophic gastritis is an important precancerous lesions of gastric cancer, but the melecular mechanism remains poorly understood. We firstly reported that loss of Slc26a9 resulted in the development and progression of gastric cancer （Liu et al., FASEB 2015). Now, we aimed to explore the role of Slc26a9 gene in the pathogenesis of CAG, which was considered as an early event of gastric cancer.Our studies demonstrated that Slc26a9 was down-regulated in the CAG and was progressive decreased in the progression of human gastric cancer. Moreover, expression of relative genes and proteins of P53, Shh, and autophagy signaling pathways were down-regulated in the Slc26a9 deficient mice when compaired with WT control. Therefore, we speculated that absence of Slc26a9 may cause the abnormalities of P53, Shh, and autophagy signaling pathways, which resulted in the disorder of gastric mucosa epithelia cell defferentiation and homeostasis, then leads to the development of CAG and malignant pathological process. In this project, two Slc26a9 deficient mouse models and Slc26a9 gene knock out cell model will be built up, together with human samples collection as well as the performance of gene chip and cell functional analysis to find out the role of Slc26a9 gene in the development and progression of CAG.