NOTCH-PAX9 signaling in alcohol-induced esophageal injury

NOTCH-PAX9 信号在酒精性食管损伤中的作用

• 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
• 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

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.

项目总结