Research Paper Volume 13, Issue 4 pp 5967—5985

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

Liwei Diao1,2, , Qinghua Zhang2, ,

  • 1 Department of Thoracic and Cardiovascular Surgery, University of Chinese Academy of Sciences Shenzhen Hospital, Shenzhen 518000, Guangdong, P.R. China
  • 2 Department of Cardiovascular Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, Heilongjiang, P.R. China

Received: November 6, 2019       Accepted: October 26, 2020       Published: February 11, 2021
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Copyright: © 2021 Diao and Zhang. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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.


BCA: bicinchoninic acid; CEC: Circulating endothelial cell; CK: Creatine kinase; CMECs: cardiac microvascular endothelial cells; DAB: diaminobenzidine; DMEM: Dulbecco's Modified Eagle's Medium; ECL: electrochemiluminescence; ELISA: Enzyme-linked immunosorbent assay; FBS: fetal bovine serum; H/R: hypoxia/reoxygenation; HDL: high-density lipoprotein; HE: hematoxylin-eosin; HRP: horseradish peroxidase; hUCMSC-ex: human umbilical cord mesenchymal stem cell-derived exosomes; I/R: ischemia-reperfusion; LAD: left anterior descending coronary artery; lncRNA: Long non-coding RNA; miR-143: microRNA-143; NC: negative control; SD: Sprague Dawley; si-UCA1: siRNA targeting UCA1; TdT: Terminal deoxyribonucleotidyl transferase; TM: thrombomodulin; VSMC: vascular smooth muscle cell; vWF: von Willebrand factor; WBCs: white blood cell.