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Journal article
Profibrotic Role of miR-154 in Pulmonary Fibrosis
American journal of respiratory cell and molecular biology, v 47(6), pp 879-887
01 Dec 2012
PMID: 23043088
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
In this study, we explored the regulation and the role of up-regulated microRNAs in idiopathic pulmonary fibrosis (IPF), a progressive interstitial lung disease of unknown origin. We analyzed the expression of microRNAs in IPF lungs and identified 43 significantly upregulated microRNAs. Twenty-four of the 43 increased microRNAs were localized to the chromosome 14q32 microRNA cluster. We validated the increased expression of miR-154, miR-134, miR-299-5p, miR-410, miR-382, miR-409-3p, miR-487b, miR-31, and miR-127 by quantitative RT-PCR and determined that they were similarly expressed in embryonic lungs. We did not find evidence for differential methylation in this region, but analysis of transcription factor binding sites identified multiple SMAD3-binding elements in the 14q32 microRNA cluster. TGF-beta 1 stimulation of normal human lung fibroblasts (NHLF) caused up-regulation of microRNAs on chr14q32 that were also increased in IPF lungs. Chromatin immunoprecipitation confirmed binding of SMAD3 to the putative promoter of miR-154. Mir-154 was increased in IPF fibroblasts, and transfection of NHLF with miR-154 caused significant increases in cell proliferation and migration. The increase in proliferation induced by TGF-beta was not observed when NHLF or IPF fibroblasts were transfected with a mir-154 inhibitor. Transfection with miR-154 caused activation of the WNT pathway in NHLF. ICG-001 and XAV939, inhibitors of the WNT/beta-catenin pathway, reduced the proliferative effect of miR-154. The potential role of miR-154, one of multiple chr14q32 microRNA cluster members up-regulated in IPF and a regulator of fibroblast migration and proliferation, should be further explored in IPF.
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Details
- Title
- Profibrotic Role of miR-154 in Pulmonary Fibrosis
- Creators
- Jadranka Milosevic - University of PittsburghKusum Pandit - University of PittsburghMarcus Magister - University of PittsburghEinat Rabinovich - University of PittsburghDaniel C. Ellwanger - Institute of Bioinformatics and Systems BiologyGuoying Yu - University of PittsburghLouis J. Vuga - University of PittsburghBenny Weksler - University of Pittsburgh Medical CenterPanayiotis V. Benos - University of PittsburghKevin F. Gibson - University of PittsburghMichael McMillan - University of Southern CaliforniaMichael Kahn - University of Southern CaliforniaNaftali Kaminski - University of Pittsburgh
- Publication Details
- American journal of respiratory cell and molecular biology, v 47(6), pp 879-887
- Publisher
- Amer Thoracic Soc
- Number of pages
- 9
- Grant note
- R01LM009657 / NATIONAL LIBRARY OF MEDICINE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Library of Medicine (NLM) Dorothy P. and Richard P. Simmons Endowed Chair for Pulmonary Research NIH RO1HL07374530; RO1HL095397; R01LM009657; RC2HL101715; RO1HL073722 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01HL095397 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Surgery
- Web of Science ID
- WOS:000314406800019
- Scopus ID
- 2-s2.0-84870508377
- Other Identifier
- 991021960805804721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology
- Respiratory System