Loss of miR-24-3p promotes epithelial cell apoptosis and impairs the recovery from intestinal inflammation.
Artin SorooshKai FangJill M HoffmanIvy K M LawElizabeth VidelockZulfiqar A LokhandwalaJonathan J ZhaoSepehr HamidiDavid M PaduaMark R FreyCharalabos PothoulakisCarl R RankinPublished in: Cell death & disease (2021)
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.
Keyphrases
- oxidative stress
- ulcerative colitis
- cell death
- cell cycle arrest
- endoplasmic reticulum stress
- weight loss
- anti inflammatory
- end stage renal disease
- newly diagnosed
- chronic kidney disease
- bariatric surgery
- type diabetes
- prognostic factors
- signaling pathway
- artificial intelligence
- body mass index
- electronic health record
- small molecule
- protein protein
- deep learning
- gastric bypass