胃食管反流病（GERD）是食管腺癌的危险因素。约40%的胃食管反流病抑酸治疗迁延不愈，挑战传统酸损伤机制。最新研究提出细胞因子介导的炎性损伤是GERD的发病机制。我们的前期实验通过转录组测序及临床组织验证发现：组织激肽释放酶基因家族（KLKs）中的KLK5在食管酸暴露异常的远端食管粘膜中的表达较无异常酸暴露的近端食管显著上调；细胞实验发现：酸性反流可增加食管上皮细胞中KLK5的表达，并促进炎症因子IL-8的分泌，形成炎症环境，并促进食管上皮细胞的增殖。因此，我们提出假说：KLK5通过刺激食管上皮细胞分泌炎症因子，形成炎症反应，并促进食管上皮细胞增殖，参与GERD的炎性损伤过程。在本项目中，我们将收集GERD患者临床标本、构建GERD细胞及动物模型，采取qPCR、Western blotting、慢病毒干扰与过表达等技术手段，进一步阐明假设，为治愈GERD、预防其炎性增生和癌变提供新思路。

Gastroesophageal reflux disease (GERD) is a risk factor for esophageal adenocarcinoma. About 40% GERD patients failed to show response to acid suppressors, which challenges the conventional pathogenesis of acid-mediated mechanism. Recent studies have raised an alternative concept that chemokines mediate inflammatory damage of esophageal tissue is the mechanism of GERD. Our preliminary study using transcriptome sequencing and esophageal tissue qPCR analysis found that the expression of tissue kallikrein 5 (KLK5) in the distal esophagus were up-regulating than that in the proximal esophagus significantly among GERD patients. We further discovered that acid exposure induced production of KLK5 and the inflammatory cytokine, IL-8. Also, acid exposure increased the proliferation of esophageal epithelial cells in vitro. Therefore we hypothesize that KLK5 activates the production of inflammatory cytokines and increases the proliferation of esophageal epithelial cells, finally resulting in inflammatory damage of esophageal tissue. In this present study, we will collect and detect the biopsy samples from GERD patients, perform experiments in vivo and in vitro using qPCR, western-blotting, interference and over-expression, etc. Once our hypothesis gets proved, we are going to contribute to the treatment of GERD and the prevention of inflammatory dysplasia and carcinogenesis.