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Research Paper|Volume 12, Issue 5|pp 4247—4267

Downregulation of lung miR-203a-3p expression by high-altitude hypoxia enhances VEGF/Notch signaling

Wei Cai1,2, Sanli Liu1,2,3, Ziquan Liu1, Shike Hou1, Qi Lv1, Huanhuan Cui1, Xue Wang4, Yuxin Zhang5, Haojun Fan1, Hui Ding1,6
  • 1School of Disaster Medical Research, Tianjin University, Tianjin 300072, China
  • 2Logistics University of Chinese People’s Armed Police Force, Tianjin 300162, China
  • 3Health Company, 95985 Troops of PLA, Kaifeng 475000, Henan province, China
  • 4Characteristic Medical Center of Chinese People’s Armed Police Force, Tianjin 300162, China
  • 5Medical Team of the Third Detachment of Beijing Armed Police Corp, Beijing 100000, China
  • 6The Second Hospital Affiliated Shaanxi University of Chinese Medicine, Shaanxi province, Xianyang 710054, China
* Equal contribution
Received: November 4, 2019Accepted: February 5, 2020Published: February 29, 2020
https://doi.org/10.18632/aging.102878

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.

Abstract

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.