Down-regulation of miR-204 attenuates endothelial-mesenchymal transition by enhancing autophagy in hypoxia-induced pulmonary hypertension.

Abstract:

:Pulmonary arterial remodeling is a crucial cause of increased pulmonary artery pressure during pulmonary hypertension (PH). Recently, growing evidence has upheld the contribution of endothelial-mesenchymal transition (EndMT) to pulmonary arterial remodeling, but the underlying mechanisms remain largely unaddressed. miR-204 has been implicated in PH, being anti-proliferative and pro-apoptotic in pulmonary artery smooth muscles cells (PASMCs), but its role in EndMT is still unknown. Here we found that miR-204 was down-regulated by hypoxia in rat pulmonary arterial intima and human pulmonary artery endothelial cells (HPAECs), and its further down-regulation by using miR-204 inhibitor suppressed hypoxia-induced EndMT. Moreover, autophagy, evoked by hypoxia in rat pulmonary arterial intima and HPAECs, suppressed hypoxia-induced EndMT via p62-dependent degradation of Snail and Twist. Additionally, autophagy was regulated by miR-204 targeting ATG7. While down-regulation of miR-204 in PASMCs reportedly promoted monocrotaline-induced pulmonary arterial hypertension via increased cell proliferation, our data suggested an important, albeit dichotomous, role of miR-204 down-regulation in endothelial cells in the process of EndMT that it attenuated EndMT by enhancing autophagy, thereby ameliorating hypoxia-induced PH to some extent.

journal_name

Eur J Pharmacol

authors

Liu T,Zou XZ,Huang N,Ge XY,Yao MZ,Liu H,Zhang Z,Hu CP

doi

10.1016/j.ejphar.2019.172673

subject

Has Abstract

pub_date

2019-11-15 00:00:00

pages

172673

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(19)30625-9

journal_volume

863

pub_type

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