Document Detail


miR-21 regulates chronic hypoxia-induced pulmonary vascular remodeling.
MedLine Citation:
PMID:  22227207     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Shanzhong Yang; Sami Banerjee; Andressa de Freitas; Huachun Cui; Na Xie; Edward Abraham; Gang Liu
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-01-06
Journal Detail:
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:
Created Date:  2012-03-16     Completed Date:  2012-07-16     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  100901229     Medline TA:  Am J Physiol Lung Cell Mol Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  L521-9     Citation Subset:  IM    
Affiliation:
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Alabama, Birmingham, USA.
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MeSH Terms
Descriptor/Qualifier:
Airway Remodeling / 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:
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:
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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