NOTCH-PAX9 signaling in alcohol-induced esophageal injury

NOTCH-PAX9 信号在酒精性食管损伤中的作用

基本信息

批准号：
10023247
负责人：
XIAOXIN Luke CHEN
金额：
$ 21.28万
依托单位：
NORTH CAROLINA CENTRAL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-25 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10023247
关键词：
Adult Affect Alcohol consumption Alcohols Binding Sites Cancer Etiology Carcinogens Cell Differentiation process Cell Nucleus Cell Proliferation Cell model Cells Cessation of life ChIP-seq Chemicals Cleaved cell Data Diet Dose Down-Regulation ES01 Embryonic Development Epithelial Epithelial Cells Epithelium Esophageal Diseases Esophageal Squamous Cell Esophageal injury Esophagus Ethanol Exposure to Foundations Future Gastroesophageal reflux disease Gene Expression Gene Expression Profile Genes Genetic Transcription Histopathology Human In Vitro Knockout Mice Ligands Liquid substance Malignant Neoplasms Malignant neoplasm of esophagus Measures Molecular Mus NOTCH1 gene Phenotype Play Population Preventive measure Reflux Risk Factors Role Signal Pathway Signal Transduction Solid Squamous Cell Squamous Epithelium Symptoms Testing Time Tissues Western Blotting alcohol effect alcohol exposure base carcinogenesis design experimental study gamma secretase in vivo inhibitor/antagonist knockout gene mouse model notch protein novel orofacial overexpression promoter transcription factor transcriptome transcriptome sequencing

项目摘要

PROJECT SUMMARY This R21 proposal is designed to use cell and mouse models to understand the role of NOTCH-PAX9 signaling pathway in alcohol-induced esophageal injury. We hypothesize that ethanol suppresses esophageal squamous cell differentiation through inhibition of the NOTCH-PAX9 signaling. We plan to test our hypothesis with two specific aims: (1) To determine whether ethanol suppresses esophageal squamous epithelial cell differentiation through inhibition of the NOTCH-PAX9 signaling. (2) To investigate whether NOTCH activation counteracts alcohol-induced esophageal injury. These studies are aimed to elucidate the role of NOTCH-PAX9 signaling in alcohol-induced esophageal injury. If proved true, it will lay down a solid mechanistic foundation to further study NOTCH activation as a novel mechanism-based preventive measure against alcohol-induced esophageal injury.

项目摘要该R21建议旨在使用单元和鼠标模型来了解Notch-Pax9信号的作用酒精引起的食管损伤的途径。我们假设乙醇抑制食道鳞状通过抑制Notch-Pax9信号传导的细胞分化。我们计划用两个具体目的：（1）确定乙醇是否抑制食管鳞状上皮细胞分化通过抑制Notch-Pax9信号传导。（2）研究Notch激活是否抵消酒精引起的食管损伤。这些研究旨在阐明Notch-Pax9信号在酒精引起的食管损伤。如果被证明是正确的，它将奠定坚实的机械基础以进一步研究Notch激活是针对酒精引起的基于机制的新型预防措施食管损伤。