Transcription factor EB modulates the homeostasis of reactive oxygen species in intestinal epithelial cells to alleviate inflammatory bowel disease.
Biochim Biophys Acta Mol Basis Dis
; 1870(5): 167065, 2024 06.
Article
in En
| MEDLINE
| ID: mdl-38342419
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.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Inflammatory Bowel Diseases
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Reactive Oxygen Species
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
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Homeostasis
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Intestinal Mucosa
Limits:
Animals
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Humans
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Male
Language:
En
Year:
2024
Type:
Article