| miR-21 regulates chronic hypoxia induced pulmonary vascular remodeling. | |
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MedLine Citation:
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PMID: 22227207 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Chronic hypoxia causes pulmonary vascular remodeling leading to pulmonary hypertension (PH) and right ventricle (RV) hypertrophy. Aberrant expression of miRNAs is closely associated with a number of pathophysiologic processes. However, the role of miRNAs in chronic hypoxia induced pulmonary vascular remodeling and PH has not been well characterized. In this study, we found increased expression of miR-21 in distal small arteries in the lungs of hypoxia exposed mice. Putative miR-21 targets, including BMPR2, WWP1, SATB1, and YOD1, were downregulated in the lungs of hypoxia exposed mice and in human pulmonary artery smooth muscle cells (PASMCs) overexpressing miR-21. We found that sequestration of miR-21, either before or after hypoxia exposure, diminished chronic hypoxia induced PH and attenuated hypoxia induced pulmonary vascular remodeling, likely through relieving the suppressed expression of miR-21 targets in the lungs of hypoxia exposed mice. Overexpression of miR-21 enhanced, whereas downregulation of miR-21 diminished the proliferation of human PASMCs in vitro and the expression of cell proliferation associated proteins, such as PCNA, Cyclin D1, and Bcl-xL. Our data suggest that miR-21 plays an important role in the pathogenesis of chronic hypoxia induced pulmonary vascular remodeling and also suggest that miR-21 is a potential target for novel therapeutics to treat chronic hypoxia associated pulmonary diseases. |
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Authors:
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Shanzhong Yang; Sami Banerjee; Andressa De Freitas; Huachun Cui; Na Xie; Edward Abraham; Gang Liu |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-6 |
Journal Detail:
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Title: American journal of physiology. Lung cellular and molecular physiology Volume: - ISSN: 1522-1504 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-9 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100901229 Medline TA: Am J Physiol Lung Cell Mol Physiol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1University of Alabama at Birmingham. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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