UMMS Affiliation
Department of Microbiology and Physiological Systems; Department of Pathology
Publication Date
2017-10-24
Document Type
Article
Disciplines
Digestive System | Digestive System Diseases | Immunology and Infectious Disease | Medical Immunology
Abstract
Understanding the transcription factors that modulate epithelial resistance to injury is necessary for understanding intestinal homeostasis and injury repair processes. Recently, transcription factor EB (TFEB) was implicated in expression of autophagy and host defense genes in nematodes and mammalian cells. However, the in vivo roles of TFEB in the mammalian intestinal epithelium were not known. Here, we used mice with a conditional deletion of Tfeb in the intestinal epithelium (Tfeb (DeltaIEC)) to examine its importance in defense against injury. Unperturbed Tfeb (DeltaIEC) mice exhibited grossly normal intestinal epithelia, except for a defect in Paneth cell granules. Tfeb (DeltaIEC) mice exhibited lower levels of lipoprotein ApoA1 expression, which is downregulated in Crohn's disease patients and causally linked to colitis susceptibility. Upon environmental epithelial injury using dextran sodium sulfate (DSS), Tfeb (DeltaIEC) mice exhibited exaggerated colitis. Thus, our study reveals that TFEB is critical for resistance to intestinal epithelial cell injury, potentially mediated by APOA1.
Keywords
Gastrointestinal models, Mucosal immunology
Rights and Permissions
© The Author(s) 2017. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
DOI of Published Version
10.1038/s41598-017-14370-4
Source
Sci Rep. 2017 Oct 24;7(1):13938. doi: 10.1038/s41598-017-14370-4. Link to article on publisher's site
Journal/Book/Conference Title
Scientific reports
Related Resources
PubMed ID
29066772
Repository Citation
Murano T, Najibi M, Paulus GL, Adiliaghdam F, Valencia-Guerrero A, Selig M, Wang X, Jeffrey K, Xavier RJ, Lassen KG, Irazoqui JE. (2017). Transcription factor TFEB cell-autonomously modulates susceptibility to intestinal epithelial cell injury in vivo. Open Access Articles. https://doi.org/10.1038/s41598-017-14370-4. Retrieved from https://escholarship.umassmed.edu/oapubs/3290
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Included in
Digestive System Commons, Digestive System Diseases Commons, Immunology and Infectious Disease Commons, Medical Immunology Commons