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

人食管肌成纤维细胞在调节 GERD 上皮反应中的作用

• 批准号: 10403963
• 负责人: Anisa Shaker
• 金额: $ 35.06万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-12 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10403963
• 关键词: 3-Dimensional; Acids; Apoptosis; Barrett Esophagus; Basal Cell; Basal Cell Hyperplasia; Biopsy; Caustic Injury; Cell Line; Chronic Disease; Coculture Techniques; Development; Disease; Economic Burden; Epithelial; Epithelial Cells; Esophageal Adenocarcinoma; Esophageal injury; Esophagitis; Esophagus; Event; Exposure to; Extracellular Space; Failure; Future; Gastroesophageal reflux disease; Healthcare Systems; Human; Hyperplasia; IL-6 inhibitor; IL8 gene; In Vitro; Inflammation; Inflammatory Response; Injury; Interleukin-6; Intestinal Metaplasia; Mediating; Mediator of activation protein; Medical; Metaplasia; Modeling; Molecular; Mucous Membrane; Myofibroblast; NF-kappa B; Operative Surgical Procedures; Organoids; Paracrine Communication; Pathogenesis; Pathway interactions; Pharmacology; Phenocopy; Phenotype; Proton Pump Inhibitors; Regulation; Research; Role; Signal Transduction; Squamous Epithelium; Stimulus; Stratified Squamous Epithelium; Stromal Cells; Testing; Therapeutic; Thick; bile salts; cellular targeting; defined contribution; gastrointestinal disorder diagnosis; human disease; injury and repair; new therapeutic target; novel; novel therapeutics; paracrine; prospective; response; single molecule; social

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.

项目总结/摘要 胃食管反流病（GERD）的并发症，如肠上皮化生（Barrett's 食管）和食管腺癌继续增加，尽管医疗和外科进步， 治疗这种管理上的缺陷部分是由于对细胞和 在GERD中介导炎症和上皮恢复的分子机制，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），一种基质细胞 在通过旁分泌介质调节上皮炎症和增殖中具有公认的作用。HEMFs 适应于三维共培养模型，该模型重现了人食管分层鳞状上皮细胞 上皮将用于研究GERD中HEMF-上皮的相互作用。该项目特别 意义重大，因为它描述了间质在GERD相关食管损伤中的作用， 这是开发这种慢性疾病的新疗法的基础。