Remote ischemic post-conditioning (RIPostC) is a technique that can protect vital organs in an indirect manner, the effects of which are exerted by the long-distance exosome-mediated transfer of functional factors. In the current study, the possible mechanism driving the function of RIPostC was explored using an in vitro system by focusing on miR-199a-5p and its downstream effectors involved in endoplasmic reticulum (ER) stress. Human umbilical vein endothelial cells (HUVECs) were administrated with hypoxia/re-oxygenation (H/R) process and exosomes were collected from the H/R-treated HUVECs. The levels of miR-199a-5p in HUVECs and exosomes were detected. Afterwards, H/R-treated SH-SY5Y neural cells was incubated with H/R HUVEC-derived exosomes, and the effect on cell apoptosis, inflammation, and miR-199a-5p-mediated ER stress was assessed. Furthermore, the key role of miR-199a-5p suppression in the protection effect of HUVEC-derived exosomes was validated by transfecting neural cells with specific inhibitor. The results showed that H/R administration increased miR-199a-5p levels both in HUVECs and exosomes. The incubation of neural cells with exosomes suppressed cell apoptosis and inflammation, and induced the level of miR-199a-5p, which led to suppressed ER stress. Moreover, the transfection of miR-199a-5p inhibitor blocked the anti-H/R function of exosomes. Taken together, the findings outlined in the current study showed that the protection effect of HUVEC derived miR-199a-5p on neural cells was exerted via exosome transfer, which then suppressed the ER stress-induced apoptosis and inflammation by targeting BIP.
Keywords: BIP; Endoplasmic reticulum (ER) stress; Ischemic stroke; Remote ischemic post-conditioning; miR-199a-5p.
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