Intestinal epithelial cell-derived exosomes package microRNA-23a-3p alleviate gut damage after ischemia/reperfusion via targeting MAP4K4

Abstract

Intestinal epithelial cells (IECs) contribute to regulation of gut injury after intestinal ischemia/reperfusion (II/R). Exosomes are well documented to deliver bioactive molecules to recipient cells for the purpose of modulating cell function. However, the role of IEC-derived exosomes in gut damage after II/R and the underlying mechanisms remain unclear. Here, we investigated the effects of exosomal miR-23a-3p on gut damage using primary IECs that underwent oxygen-glucose deprivation (OGD) as well as II/R rats. We observed that exosomes released by IECs attenuated damage in IECs that underwent OGD in vitro (P < 0.05) as well as the degree of gut injury after an II/R assault in vivo (P < 0.05). Injection of miR-23a-3p knockdown exosomes aggravated the II/R injury, whereas PF-6260933, a small-molecule inhibitor of MAP4K4, partly reversed the injury. Underlying mechanistic studies revealed that exosomal miR-23a-3p attenuated gut damage by regulating its downstream target, MAP4K4.

Keywords: Exosomes; Gut injury; Ischemia/reperfusion; MAP4K4; MiR-23a-3p.