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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
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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: |
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| Rights: | © 2019 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. | ||||||
| Divisions: | Schools > School of Science and Technology | ||||||
| Record created by: | Linda Sullivan | ||||||
| Date Added: | 30 Aug 2019 08:33 | ||||||
| Last Modified: | 30 Aug 2019 08:33 | ||||||
| URI: | https://irep.ntu.ac.uk/id/eprint/37520 |
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