Research Paper Volume 12, Issue 5 pp 4247—4267
Downregulation of lung miR-203a-3p expression by high-altitude hypoxia enhances VEGF/Notch signaling
- 1 School of Disaster Medical Research, Tianjin University, Tianjin 300072, China
- 2 Logistics University of Chinese People’s Armed Police Force, Tianjin 300162, China
- 3 Health Company, 95985 Troops of PLA, Kaifeng 475000, Henan province, China
- 4 Characteristic Medical Center of Chinese People’s Armed Police Force, Tianjin 300162, China
- 5 Medical Team of the Third Detachment of Beijing Armed Police Corp, Beijing 100000, China
- 6 The Second Hospital Affiliated Shaanxi University of Chinese Medicine, Shaanxi province, Xianyang 710054, China
received: November 4, 2019 ; accepted: February 5, 2020 ; published: February 29, 2020 ;https://doi.org/10.18632/aging.102878
How to Cite
Copyright © 2020 Cai et al. 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.
Hypoxia-related microRNAs (miRNAs) are involved in the pathogenesis of various diseases. Because potential variations in miRNA expression mediated by hypoxic lung injury at high altitude remain incompletely characterized, we used a rat model to investigate the biochemical and miRNA changes induced by high-altitude hypoxia. After 24, 48, or 72 h of hypoxic exposure, expression of VEGF/Notch pathway-related proteins were increased in rat lung tissues. Microarray screening of hypoxic lung samples revealed 57 differentially expressed miRNAs, 19 of which were related to the VEGF/Notch signaling pathway. We verified that the top downregulated miRNA (miR-203a-3p) suppresses VEGF-A translation through direct binding and also indirectly reduces Notch1, VEGFR2, and Hes1 levels, which restricts the angiogenic capacity of pulmonary microvascular endothelial cells in vitro. These findings may aid in the development of new therapeutic strategies for the prevention and treatment of hypoxic lung injury at high altitude.