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 Pharmacoljournal_title
European journal of pharmacologyauthors
Liu T,Zou XZ,Huang N,Ge XY,Yao MZ,Liu H,Zhang Z,Hu CPdoi
10.1016/j.ejphar.2019.172673subject
Has Abstractpub_date
2019-11-15 00:00:00pages
172673eissn
0014-2999issn
1879-0712pii
S0014-2999(19)30625-9journal_volume
863pub_type
杂志文章abstract::The effect of antipsychotics on electrically evoked dopamine efflux in the rat nucleus accumbens core and shell was investigated, using in vitro fast cyclic voltammetry. In the nucleus accumbens core, the dopamine D2/D3 receptor agonist, (+/-)7-OH-DPAT ((+/-)-2-dipropylamino-7-hydroxy-1,2,3,4-tetrahydronaphthalene), i...
journal_title:European journal of pharmacology
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journal_title:European journal of pharmacology
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journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2010.08.005
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journal_title:European journal of pharmacology
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journal_title:European journal of pharmacology
pub_type: 杂志文章
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journal_title:European journal of pharmacology
pub_type: 杂志文章
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journal_title:European journal of pharmacology
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journal_title:European journal of pharmacology
pub_type: 杂志文章
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journal_title:European journal of pharmacology
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journal_title:European journal of pharmacology
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journal_title:European journal of pharmacology
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journal_title:European journal of pharmacology
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pub_type: 杂志文章
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journal_title:European journal of pharmacology
pub_type: 杂志文章
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更新日期:1996-11-07 00:00:00