MicroRNA-199a Regulates Hypoxia-Mediated Pulmonary Artery Smooth Muscle Cell Proliferation and Migration by Targeting ROCK1

CHEST Journal ◽  
2015 ◽  
Vol 148 (4) ◽  
pp. 945A
Author(s):  
Jiao Yang ◽  
Xu-Wei Wu ◽  
Yan-Li Li ◽  
Yu-Xuan Zhang ◽  
Hong-Yan Zhang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Pulmonary Artery ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Smooth Muscle Cell Proliferation ◽  
Cell Proliferation And Migration ◽  
Pulmonary Artery Smooth Muscle ◽  
And Migration ◽  
Proliferation And Migration

scholarly journals MicroRNA-21 plays a role in hypoxia-mediated pulmonary artery smooth muscle cell proliferation and migration

2010 ◽  
Vol 299 (6) ◽  
pp. L861-L871 ◽  
Author(s):  
Joy Sarkar ◽  
Deming Gou ◽  
Prasanna Turaka ◽  
Ekaterina Viktorova ◽  
Ramaswamy Ramchandran ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Pulmonary Artery ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Smooth Muscle Cell Proliferation ◽  
Cell Proliferation And Migration ◽  
Pulmonary Artery Smooth Muscle ◽  
And Migration ◽  
Proliferation And Migration

Hypoxia stimulates pulmonary artery smooth muscle cell (PASMC) proliferation. Recent studies have implicated an important role for microRNAs (miRNAs) in hypoxia-mediated responses in various cellular processes, including cell proliferation. In this study, we investigated the role of microRNA-21 (miR-21) in hypoxia-induced PASMC proliferation and migration. We first demonstrated that miR-21 expression increased by ∼3-fold in human PASMC after 6 h of hypoxia (3% O2) and remained high (∼2-fold) after 24 h of hypoxia. Knockdown of miR-21 with anti-miR-21 inhibitors significantly reduced hypoxia-induced cell proliferation, whereas miR-21 overexpression in normoxia enhanced cell proliferation. We also found that miR-21 is essential for hypoxia-induced cell migration. Protein expression of miR-21 target genes, specifically programmed cell death protein 4 (PDCD4), Sprouty 2 (SPRY2), and peroxisome proliferator-activated receptor-α (PPARα), was decreased in hypoxia and in PASMC overexpressing miR-21 in normoxia and increased in hypoxic cells in which miR-21 was knocked down. In addition, PPARα 3′-untranslated region (UTR) luciferase-based reporter gene assays demonstrated that PPARα is a direct target of miR-21. Taken together, our findings indicate that miR-21 plays a significant role in hypoxia-induced pulmonary vascular smooth muscle cell proliferation and migration by regulating multiple gene targets.

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