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Updated: Sep 15, 2025
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Analyzing Beneficial Effects of Nutritional Supplements on Intestinal Epithelial Barrier Functions During Experimental Colitis
Published on: January 5, 2017
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Intestinal Epithelial-Derived USP13 Alleviates Colonic Inflammation by Suppressing GRP78-mediated Endoplasmic
Chenchen Qian1,2, Chenghong Hu1, Yong Xu1
1School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|July 18, 2025
Summary
Ubiquitin-specific peptidase 13 (USP13) protects against inflammatory bowel disease (IBD) by reducing endoplasmic reticulum stress and apoptosis. Restoring USP13 in the gut may offer a new therapy for IBD patients.
Area of Science:
- Gastroenterology
- Molecular Biology
- Cell Biology
Background:
- Inflammatory bowel disease (IBD) involves endoplasmic reticulum (ER) stress and intestinal epithelial cell apoptosis.
- Deubiquitinases and E3 ubiquitin ligases critically regulate protein ubiquitination in IBD pathogenesis.
Purpose of the Study:
- To investigate the role of deubiquitinase USP13 in a DSS-induced colitis mouse model.
- To explore the underlying molecular mechanisms of USP13 in maintaining intestinal health.
Main Methods:
- Generated intestinal epithelial-specific Usp13 knockout (USP13^IEKO) mice.
- Induced colitis using DSS and utilized adeno-associated virus serotype 9 (AAV9) for USP13 overexpression.
- Analyzed ER stress, apoptosis, and intestinal barrier integrity.
Main Results:
- USP13 knockout exacerbated DSS-induced colitis, increasing ER stress and apoptosis.
- USP13 interacts with GRP78, attenuating ER stress-induced apoptosis via K63-linked ubiquitination.
- AAV9-mediated USP13 restoration ameliorated colitis and preserved intestinal barrier integrity.
- Reduced USP13 levels were observed in ulcerative colitis patients.
Conclusions:
- USP13 plays a protective role in IBD by modulating the USP13-GRP78 axis and mitigating ER stress.
- Targeting USP13 via intestinal epithelial-specific gene therapy presents a potential therapeutic strategy for IBD.
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