1. The mRNA-binding protein IGF2BP1 maintains intestinal barrier function by up-regulating occludin expression.
- Author
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Singh V, Gowda CP, Singh V, Ganapathy AS, Karamchandani DM, Eshelman MA, Yochum GS, Nighot P, and Spiegelman VS
- Subjects
- Animals, Cell Line, Colitis chemically induced, Colitis mortality, Colitis pathology, Colon pathology, Humans, Intestinal Mucosa cytology, Intestinal Mucosa metabolism, Mice, Mice, Inbred C57BL, Mice, Transgenic, Occludin genetics, Protein Binding, RNA Interference, RNA, Messenger metabolism, RNA, Small Interfering metabolism, RNA-Binding Proteins antagonists & inhibitors, RNA-Binding Proteins genetics, Severity of Illness Index, Survival Rate, Tight Junction Proteins metabolism, Up-Regulation, Occludin metabolism, Permeability, RNA-Binding Proteins metabolism
- Abstract
Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) is an mRNA-binding protein that has an oncofetal pattern of expression. It is also expressed in intestinal tissue, suggesting that it has a possible role in intestinal homeostasis. To investigate this possibility, here we generated Villin CreERT2:Igf2bp1flox/flox mice, which enabled induction of an IGF2BP1 knockout specifically in intestinal epithelial cells (IECs) of adult mice. Using gut barrier and epithelial permeability assays and several biochemical approaches, we found that IGF2BP1 ablation in the adult intestinal epithelium causes mild active colitis and mild-to-moderate active enteritis. Moreover, the IGF2BP1 deletion aggravated dextran sodium sulfate-induced colitis. We also found that IGF2BP1 removal compromises barrier function of the intestinal epithelium, resulting from altered protein expression at tight junctions. Mechanistically, IGF2BP1 interacted with the mRNA of the tight-junction protein occludin (Ocln), stabilizing Ocln mRNA and inducing expression of occludin in IECs. Furthermore, ectopic occludin expression in IGF2BP1-knockdown cells restored barrier function. We conclude that IGF2BP1-dependent regulation of occludin expression is an important mechanism in intestinal barrier function maintenance and in the prevention of colitis., Competing Interests: Conflict of interest—The authors declare that they have no conflicts of interest with the contents of this article., (© 2020 Singh et al.)
- Published
- 2020
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