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Propionate Enhances Cell Speed and Persistence to Promote Intestinal Epithelial Turnover and Repair.

Authors
  • Bilotta, Anthony J1
  • Ma, Chunyan2
  • Yang, Wenjing1
  • Yu, Yanbo1
  • Yu, Yu1
  • Zhao, Xiaojing1
  • Zhou, Zheng1
  • Yao, Suxia1
  • Dann, Sara M3
  • Cong, Yingzi4
  • 1 Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas.
  • 2 Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas; Department of Central Laboratory, Shandong Provincial Hospital Shandong First Medical University, Jinan, China. , (China)
  • 3 Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas.
  • 4 Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas; Department of Pathology, University of Texas Medical Branch, Galveston, Texas. Electronic address: [email protected]
Type
Published Article
Journal
Cellular and Molecular Gastroenterology and Hepatology
Publisher
Elsevier
Publication Date
Nov 22, 2020
Identifiers
DOI: 10.1016/j.jcmgh.2020.11.011
PMID: 33238220
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Gut bacteria-derived short-chain fatty acids (SCFAs) play crucial roles in the maintenance of intestinal homeostasis. However, how SCFAs regulate epithelial turnover and tissue repair remain incompletely understood. In this study, we investigated how the SCFA propionate regulates cell migration to promote epithelial renewal and repair. Mouse small intestinal epithelial cells (MSIE) and human Caco-2 cells were used to determine the effects of SCFAs on gene expression, proliferation, migration, and cell spreading in vitro. Video microscopy and single cell tracking were used to assess cell migration kinetically. 5-bromo-2'-deoxyuridine (BrdU) and hydroxyurea were used to assess the effects of SCFAs on migration in vivo. Lastly, an acute colitis model using dextran sulfate sodium (DSS) was used to examine the effects of SCFAs in vivo. Using video microscopy and single cell tracking, we found that propionate promoted intestinal epithelial cell migration by enhancing cell spreading and polarization, which led to increases in both cell speed and persistence. This novel function of propionate was dependent on inhibition of class I histone deacetylases (HDAC) and GPR43 and required signal transducer and activator of transcription 3 (STAT3). Furthermore, using 5-bromo-2'-deoxyuridine (BrdU) and hydroxyurea in vivo, we found that propionate enhanced cell migration up the crypt-villus axis under homeostatic conditions, while also protecting against ulcer formation in experimental colitis. Our results demonstrate a mechanism by which propionate stimulates cell migration in an HDAC inhibition, GPR43, and STAT3 dependent manner, and suggest that propionate plays an important role in epithelial migration independent of proliferation. Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

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