Intestinal epithelial cell-derived exosomes package microRNA-23a-3p alleviate gut damage after ischemia/reperfusion via targeting MAP4K4 - 20/04/22
, Hui Yang c, ⁎ 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.
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Highlights |
• | Intestinal epithelial cell (IEC)-derived exosomes reduce the damage of IECs. |
• | IEC-derived exosomes decrease the intestinal ischemia-reperfusion (II/R) injury. |
• | Exosomal miR-23a-3p secreted by IECs alleviates the II/R injury. |
• | Exosomal miR-23a-3p reduces the II/R injury by regulating MAP4K4. |
Abbreviations : miRNA, II/R, IEC, MAP4K4, SMA, TJ, TNF-α, OGD, GoCI2, ZO-1, TEM, NTA, LDH, MTT, DMSO, PBS, ELISA, HE, HRP
Keywords : Exosomes, MiR-23a-3p, MAP4K4, Ischemia/reperfusion, Gut injury
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Vol 149
Articolo 112810- maggio 2022 Ritorno al numero
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