The role of human esophageal myofibroblasts in regulating the epithelial response in GERD

项目摘要/摘要 胃食道反流病(GERD)的并发症，如肠化生(Barrett‘s 食道癌)和食管腺癌继续增加，尽管内科和外科技术有了进步 治疗。这种管理上的赤字部分是由于对细胞和 介导GERD炎症和上皮修复的分子机制而不是进展为 化生。该项目的重点将是人食管肌成纤维细胞(HEMF)，这是一种基质细胞 具有公认的作用，通过旁分泌介质调节上皮炎症和增殖。HEMF 改编成三维共培养模型，概括了人类食管层状鳞状细胞 上皮细胞将被用来研究HEMF-GERD中上皮细胞之间的相互作用。这个项目特别是 意义重大，因为它描述了间质在GERD相关性食道损伤中鲜为人知的作用，并 这是为这种慢性疾病开发新疗法的基础。

PROJECT SUMMARY/ABSTRACT Complications of gastro-esophageal reflux disease (GERD) such as intestinal metaplasia (Barrett’s esophagus) and esophageal adenocarcinoma continue to increase despite advances in medical and surgical therapies. This deficit in management is due in part to the incomplete understanding of the cellular and molecular mechanisms that mediate inflammation and epithelial restitution in GERD rather than progression to metaplasia. The focus of the project will be on the human esophageal myofibroblast (HEMF), a stromal cell with a recognized role in regulation of epithelial inflammation and proliferation via paracrine mediators. HEMFs adapted into three dimensional co-culture models that recapitulate human esophageal stratified squamous epithelium will be used to investigate HEMF-epithelial interactions in GERD. This project is particularly significant because it delineates the poorly understood role of stroma in GERD related esophageal injury and is the basis for the development of novel therapeutics for this chronic disorder.