Open Access

Downregulation of miR‑98 contributes to hypoxic pulmonary hypertension by targeting ALK1

  • Authors:
    • Qingling Li
    • Xincan Zhou
    • Xianghui Zhou
  • View Affiliations

  • Published online on: July 9, 2019     https://doi.org/10.3892/mmr.2019.10482
  • Pages: 2167-2176
  • Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Chronic hypoxia is one of the most common causes of secondary pulmonary hypertension, the mechanisms of which remain unclear. MicroRNAs (miRNAs) are small, noncoding RNAs that inhibit the translation or accelerate the degradation of mRNA. Previous studies have demonstrated that deregulated miRNA expression contributes to various cellular processes including cell apoptosis and proliferation, which are mediated by hypoxia. In the present study, the expression of miR‑98 was identified to be decreased in the lung tissue of a hypoxic pulmonary hypertension (HPH) rat model and pulmonary artery (PA) smooth muscle cells (PASMCs), which was induced by hypoxia. By transfecting miR‑98 mimics into PASMCs, the high expression of miR‑98 inhibited cell proliferation, but upregulated hypoxia‑induced PASMCs apoptosis. However, these effects of miR‑98 mimics on PASMCs were reversed by ALK1 (activin receptor‑like kinase‑1) overexpression. ALK1 was identified as a candidate target of miR‑98. In addition, overexpressing miR‑98 markedly decreased the pulmonary artery wall thickness and the right ventricular systolic pressure in rats induced by hypoxia. These results provided clear evidence that miR‑98 was a direct regulator of ALK1, and that the downregulation of miR‑98 contributed to the pathogenesis of HPH. These results provide a novel potential therapeutic strategy for the treatment of HPH.

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Copy and paste a formatted citation
APA
Li, Q., Zhou, X., & Zhou, X. (2019). Downregulation of miR‑98 contributes to hypoxic pulmonary hypertension by targeting ALK1. Molecular Medicine Reports, 20, 2167-2176. https://doi.org/10.3892/mmr.2019.10482
MLA
Li, Q., Zhou, X., Zhou, X."Downregulation of miR‑98 contributes to hypoxic pulmonary hypertension by targeting ALK1". Molecular Medicine Reports 20.3 (2019): 2167-2176.
Chicago
Li, Q., Zhou, X., Zhou, X."Downregulation of miR‑98 contributes to hypoxic pulmonary hypertension by targeting ALK1". Molecular Medicine Reports 20, no. 3 (2019): 2167-2176. https://doi.org/10.3892/mmr.2019.10482