miR-24 is elevated in ulcerative colitis patients and regulates intestinal epithelial barrier function

Soroosh, A., Rankin, C.R., Polytarchou, C. ORCID: 0000-0002-1948-7934, Lokhandwala, Z.A., Patel, A., Chang, L., Pothoulakis, C., Iliopoulos, D. and Padua, D.M., 2019. miR-24 is elevated in ulcerative colitis patients and regulates intestinal epithelial barrier function. The American Journal of Pathology, 189 (9), pp. 1763-1774. ISSN 0002-9440

[img]
Preview
Text
14688_Polytarchou.pdf - Published version

Download (2MB) | Preview

Abstract

Inflammatory bowel disease is characterized by high levels of inflammation and loss of barrier integrity in the colon. The intestinal barrier is a dynamic network of proteins that encircle intestinal epithelial cells. miRNAs regulate protein-coding genes. In this study, miR-24 was found to be elevated in colonic biopsies and blood samples from ulcerative colitis (UC) patients compared with healthy controls. In the colon of UC patients, miR-24 is localized to intestinal epithelial cells, which prompted an investigation of intestinal epithelial barrier function. Two intestinal epithelial cell lines were used to study the effect of miR-24 overexpression on barrier integrity. Overexpression of miR-24 in both cell lines led to diminished transepithelial electrical resistance and increased dextran flux, suggesting an effect on barrier integrity. Overexpression of miR-24 did not induce apoptosis or affect cell proliferation, suggesting that the effect of miR-24 on barrier function was due to an effect on cell–cell junctions. Although the tight junctions in cells overexpressing miR-24 appeared normal, miR-24 overexpression led to a decrease in the tight junction–associated protein cingulin. Loss of cingulin compromised barrier formation; cingulin levels negatively correlated with disease severity in UC patients. Together, these data suggest that miR-24 is a significant regulator of intestinal barrier that may be important in the pathogenesis of UC.

Item Type: Journal article
Publication Title: The American Journal of Pathology
Creators: Soroosh, A., Rankin, C.R., Polytarchou, C., Lokhandwala, Z.A., Patel, A., Chang, L., Pothoulakis, C., Iliopoulos, D. and Padua, D.M.
Publisher: Elsevier
Date: September 2019
Volume: 189
Number: 9
ISSN: 0002-9440
Identifiers:
NumberType
10.1016/j.ajpath.2019.05.018DOI
S0002944019300896Publisher Item Identifier
Rights: © 2019 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
Divisions: Schools > School of Science and Technology
Depositing User: Linda Sullivan
Date Added: 30 Aug 2019 08:33
Last Modified: 30 Aug 2019 08:33
URI: http://irep.ntu.ac.uk/id/eprint/37520

Actions (login required)

Edit View Edit View

Views

Views per month over past year

Downloads

Downloads per month over past year