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Soroosh A, Fang K, Hoffman JM, et al. Loss of miR-24-3p promotes epithelial cell apoptosis and impairs the recovery from intestinal inflammation. Cell Death Dis. 2021;13(1):8doi: 10.1038/s41419-021-04463-4.
Soroosh, A., Fang, K., Hoffman, J. M., Law, I. K. M., Videlock, E., Lokhandwala, Z. A., Zhao, J. J., Hamidi, S., Padua, D. M., Frey, M. R., Pothoulakis, C., & Rankin, C. R. (2021). Loss of miR-24-3p promotes epithelial cell apoptosis and impairs the recovery from intestinal inflammation. Cell death & disease, 13(1), 8. https://doi.org/10.1038/s41419-021-04463-4
Soroosh, Artin, et al. "Loss of miR-24-3p promotes epithelial cell apoptosis and impairs the recovery from intestinal inflammation." Cell death & disease vol. 13,1 (2021): 8. doi: https://doi.org/10.1038/s41419-021-04463-4
Soroosh A, Fang K, Hoffman JM, Law IKM, Videlock E, Lokhandwala ZA, Zhao JJ, Hamidi S, Padua DM, Frey MR, Pothoulakis C, Rankin CR. Loss of miR-24-3p promotes epithelial cell apoptosis and impairs the recovery from intestinal inflammation. Cell Death Dis. 2021 Dec 18;13(1):8. doi: 10.1038/s41419-021-04463-4. PMID: 34923573.
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Cell Death Dis. 2021 Dec 18;13(1):8. doi: 10.1038/s41419-021-04463-4.

Loss of miR-24-3p promotes epithelial cell apoptosis and impairs the recovery from intestinal inflammation.

Cell death & disease

Artin Soroosh, Kai Fang, Jill M Hoffman, Ivy K M Law, Elizabeth Videlock, Zulfiqar A Lokhandwala, Jonathan J Zhao, Sepehr Hamidi, David M Padua, Mark R Frey, Charalabos Pothoulakis, Carl R Rankin

Affiliations

  1. Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
  2. Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, CA, USA.
  3. The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA, USA.
  4. Department of Pediatrics and Department of Biochemistry and Molecular Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
  5. Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, University of California Los Angeles, Los Angeles, CA, USA. [email protected].

PMID: 34923573 DOI: 10.1038/s41419-021-04463-4

Abstract

While apoptosis plays a significant role in intestinal homeostasis, it can also be pathogenic if overactive during recovery from inflammation. We recently reported that microRNA-24-3p (miR-24-3p) is elevated in the colonic epithelium of ulcerative colitis patients during active inflammation, and that it reduced apoptosis in vitro. However, its function during intestinal restitution following inflammation had not been examined. In this study, we tested the influence of miR-24-3p on mucosal repair by studying recovery from colitis in both novel miR-24-3p knockout and miR-24-3p-inhibited mice. We observed that knockout mice and mice treated with a miR-24-3p inhibitor had significantly worsened recovery based on weight loss, colon length, and double-blinded histological scoring. In vivo and in vitro analysis of miR-24-3p inhibition in colonic epithelial cells revealed that inhibition promotes apoptosis and increases levels of the pro-apoptotic protein BIM. Further experiments determined that silencing of BIM reversed the pro-apoptotic effects of miR-24-3p inhibition. Taken together, these data suggest that miR-24-3p restrains intestinal epithelial cell apoptosis by targeting BIM, and its loss of function is detrimental to epithelial restitution following intestinal inflammation.

© 2021. The Author(s).

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