Back to Search
Start Over
Transcription factor EB modulates the homeostasis of reactive oxygen species in intestinal epithelial cells to alleviate inflammatory bowel disease.
- Source :
-
Biochimica et biophysica acta. Molecular basis of disease [Biochim Biophys Acta Mol Basis Dis] 2024 Jun; Vol. 1870 (5), pp. 167065. Date of Electronic Publication: 2024 Feb 09. - Publication Year :
- 2024
-
Abstract
- Transcription factor EB (TFEB), a master lysosomal biogenesis and autophagy regulator, is crucial for cellular homeostasis, and its abnormality is related to diverse inflammatory diseases. Genetic variations in autophagic genes are associated with susceptibility to inflammatory bowel disease (IBD); however, little is known about the role and mechanism of TFEB in disease pathogenesis. In this study, we found that the genetic deletion of TFEB in mouse intestinal epithelial cells (IEC) caused intestinal barrier dysfunction, leading to increased susceptibility to experimental colitis. Mechanistically, TFEB functionally protected IEC in part through peroxisome proliferator-activated receptor gamma coactivator 1alpha (TFEB-PGC1α axis) induction, which consequently suppressed reactive oxygen species. TFEB can directly regulate PGC-1α transcription to control antioxidation level. Notably, TFEB expression is impaired and downregulated in the colon tissues of IBD patients. Collectively, our results indicate that intestinal TFEB participates in oxidative stress regulation and attenuates IBD progression.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. This work is supported by the National Natural Science Foundation of China (82070846, 31571165 and 31771288), Chengdu Science and Technology Program (2023-GH02-00083-HZ), and EFSD and Lilly EXPLORING AND APPLYING NEW STRATEGIES IN DIABETES (EXPAND) Programme.<br /> (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Mice
Humans
Oxidative Stress
Epithelial Cells metabolism
Epithelial Cells pathology
Mice, Inbred C57BL
Mice, Knockout
Male
Colitis metabolism
Colitis pathology
Colitis chemically induced
Colitis genetics
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors metabolism
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors genetics
Reactive Oxygen Species metabolism
Inflammatory Bowel Diseases metabolism
Inflammatory Bowel Diseases pathology
Inflammatory Bowel Diseases genetics
Homeostasis
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha metabolism
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha genetics
Intestinal Mucosa metabolism
Intestinal Mucosa pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1879-260X
- Volume :
- 1870
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Biochimica et biophysica acta. Molecular basis of disease
- Publication Type :
- Academic Journal
- Accession number :
- 38342419
- Full Text :
- https://doi.org/10.1016/j.bbadis.2024.167065