禁食诱导的小肠上皮细胞辐射防护机制-猫眼课题宝

禁食诱导的小肠上皮细胞辐射防护机制

批准号：

10645872

负责人：

HELEN M PIWNICA-WORMS

金额：

$66.15万

依托单位：

UNIVERSITY OF TX MD ANDERSON CAN CTR

依托单位国家：

美国

项目类别：

财政年份：

2023

资助国家：

美国

项目状态：

未结题

起止时间：

2023-06-01 至 2028-05-31

来源：

https://reporter.nih.gov/project-details/10645872

关键词：

3-hydroxy-3-methylglutaryl-coenzyme A Animals Automobile Driving Bacteria Cancer Patient Cell Separation Cells ChIP-seq Chromatin Clinical Coenzyme A Data Dose Enhancers Epigenetic Process Epithelial Cells Fasting Gene Expression Genes Genetic Transcription Goals HDAC4 gene Histone H3 Histone H4 Intestines Ionizing radiation Ketone Bodies Knock-out Lysine Malignant neoplasm of pancreas Mediating Metabolic Mus Normal tissue morphology Organ Outcome Patients Probiotics Production Quality of life Radiation Radiation Dose Unit Radiation Protection Radiation Toxicity Radiation induced damage Radiation therapy Reaction Regimen Resolution Small Intestinal Goblet Cell Small Intestines Testing Toxic effect beta-Hydroxybutyrate cell killing epigenome epigenomics experimental study gastrointestinal gut microbiome improved insight intestinal crypt intestinal homeostasis ketogenesis microbial microbiome alteration mimetics mouse model neoplastic cell novel pancreas radiation therapy preservation programs promoter protective effect radioprotected repaired response side effect single cell analysis stem cells transcriptome sequencing

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中文摘要

翻译

项目摘要我们证明，短期禁食保护小鼠免受高剂量电离辐射，通过保护小细胞，肠（SI）干细胞，从而保持SI稳态和促进有机体存活。我们也表明禁食产生的主要酮体直接修饰SI上皮细胞的表观基因组，诱导基因表达变化和禁食改变肠道微生物组，已知代谢物诱导表观遗传和基因表达变化。我们将检验这个假设，酮体和微生物代谢物引起的禁食，引起表观遗传和基因表达的变化， SI上皮细胞，从而提供GI辐射防护。

英文摘要

Project Summary We demonstrated that short-term fasting protects mice from high dose ionizing radiation by protecting small intestinal (SI) stem cells, thereby preserving SI homeostasis and promoting organismal survival. We also showed that the major ketone body produced by fasting directly modifies the epigenome of SI epithelial cells to induce gene expression changes and that fasting alters the gut microbiome to favor bacteria whose metabolites are known to induce epigenetic and gene expression changes. We will test the hypothesis that ketone bodies and microbial metabolites induced by fasting, cause epigenetic and gene expression changes in SI epithelial cells thereby providing GI radioprotection.

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