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Original Research |

MicroRNA-199a-5p Is Associated With Hypoxia-Inducible Factor-1α Expression in Lungs From Patients With COPDmiR199a-5p Expression in Patients With COPD

Shiro Mizuno, MD, PhD; Harm J. Bogaard, MD, PhD; Jose Gomez-Arroyo, MD; Aysar Alhussaini, MD; Donatas Kraskauskas, DVM; Carlyne D. Cool, MD; Norbert F. Voelkel, MD
Author and Funding Information

From the Victoria Johnson Center for Obstructive Lung Diseases (Drs Mizuno, Bogaard, Gomez-Arroyo, Alhussaini, Kraskauskas, and Voelkel), Virginia Commonwealth University, Richmond, VA; the Division of Respiratory Disease (Dr Mizuno), Kanazawa Medical University, Ishikawa, Japan; the VU University Medical Center (Dr Bogaard), Amsterdam, The Netherlands; and the Department of Pathology (Dr Cool), University of Colorado Health Science Center, Lung Tissue Repository Consortium Repository, Aurora, CO.

Correspondence to: Norbert F. Voelkel, MD, Virginia Commonwealth University, Molecular Medicine Research Bldg, Broad St, Richmond, VA 23220; e-mail: nvoelkel@mcvh-vcu.edu


Funding/Support: This study was supported by the National Institutes of Health [Grant N01-HR-46160-3], and funds from the Victoria Johnson Center for Lung Research of the Virginia Commonwealth University.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2012;142(3):663-672. doi:10.1378/chest.11-2746
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Background:  MicroRNAs (miRNAs) are small noncoding RNAs that silence target gene expression posttranscriptionally, and their impact on gene expression has been reported in various diseases. It has been reported that the expression of the hypoxia-inducible factor-1α (HIF-1α) is reduced and that of p53 is increased in lungs from patients with COPD. However, the role of miRNAs associated with these genes in lungs from patients with COPD is unknown.

Methods:  Lung tissue samples from 55 patients were included in this study. Total RNA, miRNA, and protein were extracted from lung tissues and used for reverse transcriptase polymerase chain reaction and Western blot analysis. Cell culture experiments were performed using cultured human pulmonary microvascular endothelial cells (HPMVECs).

Results:  miR-34a and miR-199a-5p expressions were increased, and the phosphorylation of AKT was decreased in the lung tissue samples of patients with COPD. The miR-199a-5p expression was correlated with HIF-1α protein expression in the lungs of patients with COPD. Transfection of HPMVECs with the miR-199a-5p precursor gene decreased HIF-1α protein expression, and transfection with the miR-34a precursor gene increased miR-199a-5p expression.

Conclusions:  These data suggest that miR-34a and miR-199a-5p contribute to the pathogenesis of COPD, and these miRNAs may also affect the HIF-1α-dependent lung structure maintenance program.

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