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Upregulated Tβ4 expression in inflammatory bowel disease impairs the intestinal mucus barrier by inhibiting autophagy in mice.
- Source :
-
Experimental cell research [Exp Cell Res] 2024 Jan 01; Vol. 434 (1), pp. 113871. Date of Electronic Publication: 2023 Dec 02. - Publication Year :
- 2024
-
Abstract
- Disrupted intestinal barrier homeostasis is fundamental to inflammatory bowel disease. Thymosin β4 (Tβ4) improves inflammation and has beneficial effects in dry-eye diseases, but its effects on the intestinal mucus barrier remain unknown. Therefore, this study evaluated the underlying regulatory mechanisms and effects of Tβ4 by examining Tβ4 expression in a mouse model with dextran sodium sulfate (DSS)-induced colitis and colonic barrier damage. Additionally, we intraperitoneally injected C57BL/6 mice with Tβ4 to assess barrier function, microtubule-associated protein 1 light chain 3 (LC3II) protein expression, and autophagy. Finally, normal human colon tissue and colon carcinoma cells (Caco2) were cultured to verify Tβ4-induced barrier function and autophagy changes. Mucin2 levels decreased, microbial infiltration increased, and Tβ4 expression increased in the colitis mouse model versus the control mice, indicating mucus barrier damage. Moreover, Tβ4-treated C57BL/6 mice had damaged intestinal mucus barriers and decreased LC3II levels. Tβ4 also inhibited colonic mucin2 production, disrupted tight junctions, and downregulated autophagy; these results were confirmed in Caco2 cells and normal human colon tissue. In summary, Tβ4 may be implicated in colitis by compromising the integrity of the intestinal mucus barrier and inhibiting autophagy. Thus, Tβ4 could be a new diagnostic marker for intestinal barrier defects.<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.<br /> (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Female
Humans
Mice
Autophagy drug effects
Cell Line, Tumor
Colitis metabolism
Colitis pathology
Colon metabolism
Colon pathology
Mice, Inbred C57BL
Sirolimus administration & dosage
Up-Regulation
Inflammatory Bowel Diseases metabolism
Inflammatory Bowel Diseases pathology
Thymosin genetics
Thymosin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2422
- Volume :
- 434
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Experimental cell research
- Publication Type :
- Academic Journal
- Accession number :
- 38049080
- Full Text :
- https://doi.org/10.1016/j.yexcr.2023.113871