Transfer of lncRNA UCA1 by hUCMSCs-derived exosomes protects against hypoxia/reoxygenation injury through impairing miR-143-targeted degradation of Bcl-2.

Ischemia results in neuronal damage via alterations in gene transcription and protein expression. Long noncoding RNAs (LncRNAs) are pivotal in the regulation of target protein expression in hypoxia/reoxygenation (H/R). In this study, we observed the function of exosomes-carried lncRNA UCA1 in H/R-induced injury of cardiac microvascular endothelial cells (CMECs). In H/R cell model, CMECs were co-cultured with human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-ex). The loss-of-function experiments were conducted to assess the effect of lncRNA UCA1 on H/R injury by assessing the biological behaviors of CMECs. The relationship among lncRNA UCA1, miR-143 and Bcl-2 were verified. An ischemia-reperfusion (I/R) rat model was established. Then hUCMSC-ex was injected into I/R rats to identify its effects on apoptosis and autophagy. Functional rescue experiments were performed to verify the sponge system. In vitro and in vivo experiments showed that hUCMSC-ex protected I/R rats and H/R CMECs against injury. Silencing UCA1 in hUCMSC-ex or miR-143 overexpression aggravated H/R injury in CMECs. LncRNA UCA1 competitively bound to miR-143 to upregulate Bcl-2. And hUCMSCs-ex/si-UCA1+inhi-miR-143 treatment protected CMECs against H/R injury and inhibited hyperautophagy. Together, hUCMSC-ex-derived lncRNA UCA1 alleviates H/R injury through the miR-143/Bcl-2/Beclin-1 axis. Hence, this study highlights a stem cell-based approach against I/R injury.