| miR-21 regulates chronic hypoxia-induced pulmonary vascular remodeling. | |
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MedLine Citation:
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PMID: 22227207 Owner: NLM Status: MEDLINE |
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 microRNA (miRNA) 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 bone morphogenetic protein receptor (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 proliferating cell nuclear antigen, 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; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-01-06 |
Journal Detail:
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Title: American journal of physiology. Lung cellular and molecular physiology Volume: 302 ISSN: 1522-1504 ISO Abbreviation: Am. J. Physiol. Lung Cell Mol. Physiol. Publication Date: 2012 Mar |
Date Detail:
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Created Date: 2012-03-16 Completed Date: 2012-07-16 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 100901229 Medline TA: Am J Physiol Lung Cell Mol Physiol Country: United States |
Other Details:
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Languages: eng Pagination: L521-9 Citation Subset: IM |
Affiliation:
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Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Alabama, Birmingham, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Airway Remodeling
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genetics,
physiology* Animals Anoxia / complications, genetics, metabolism, physiopathology* Apoptosis / genetics Bone Morphogenetic Protein Receptors, Type II / genetics, metabolism Cell Cycle Proteins / genetics Cell Line Cell Proliferation Cyclin D1 / genetics, metabolism Down-Regulation / genetics Humans Hypertension, Pulmonary / etiology, genetics, metabolism, physiopathology Hypertrophy, Right Ventricular / genetics, metabolism, physiopathology Lung / metabolism, physiopathology* Matrix Attachment Region Binding Proteins / genetics, metabolism Mice MicroRNAs / genetics* Muscle, Smooth, Vascular / metabolism, physiopathology* Myocytes, Smooth Muscle / metabolism, pathology* Pulmonary Artery / metabolism, physiopathology Ubiquitin-Protein Ligases / genetics, metabolism Up-Regulation / genetics bcl-X Protein / genetics, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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HL-076206/HL/NHLBI NIH HHS; HL-097218/HL/NHLBI NIH HHS; HL-105473/HL/NHLBI NIH HHS; R01 HL105473/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/BCL2L1 protein, human; 0/CCND1 protein, human; 0/Cell Cycle Proteins; 0/MIRN21 microRNA, mouse; 0/Matrix Attachment Region Binding Proteins; 0/MicroRNAs; 0/Satb1 protein, mouse; 0/bcl-X Protein; 136601-57-5/Cyclin D1; EC 2.7.11.30/Bmpr2 protein, mouse; EC 2.7.11.30/Bone Morphogenetic Protein Receptors, Type II; EC 6.3.2.19/Ubiquitin-Protein Ligases; EC 6.3.2.19/WWP1 protein, mouse |
| Comments/Corrections | |
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