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MicroRNA‐21 plays a Role in Hypoxia‐mediated Pulmonary Artery Smooth Muscle Cell Proliferation and Migration
Author(s) -
Sarkar Joy,
Gou Deming,
Ramchandran Ramaswamy,
Raj Usha
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.861.9
Subject(s) - hypoxia (environmental) , cell growth , microrna , gene knockdown , microbiology and biotechnology , biology , cell , cell migration , cancer research , chemistry , gene , biochemistry , organic chemistry , oxygen
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 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% O 2 ) 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 over‐expression 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 Alpha (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′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.