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Cited by 935Interstitial Lung Diseases and Idiopathic Pulmonary FibrosisMicroRNA in disease regulationPulmonary Hypertension Research and Treatments

miR-21 mediates fibrogenic activation of pulmonary fibroblasts and lung fibrosis

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Liu, Gang, Friggeri, Arnaud, Yang, Yanping, Milosevic, Jadranka, Ding, Qiang, Thannickal, Victor J., Kaminski, Naftali, Abraham, Edward·2010·Journal of Experimental Medicine
DOI 10.1084/jem.20100035PMC PMC2916139
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Abstract

Uncontrolled extracellular matrix production by fibroblasts in response to tissue injury contributes to fibrotic diseases, such as idiopathic pulmonary fibrosis (IPF), a progressive and ultimately fatal process that currently has no cure. Although dysregulation of miRNAs is known to be involved in a variety of pathophysiologic processes, the role of miRNAs in fibrotic lung diseases is unclear. In this study, we found up-regulation of miR-21 in the lungs of mice with bleomycin-induced fibrosis and also in the lungs of patients with IPF. Increased miR-21 expression was primarily localized to myofibroblasts. Administration of miR-21 antisense probes diminished the severity of experimental lung fibrosis in mice, even when treatment was started 5-7 d after initiation of pulmonary injury. TGF-beta1, a central pathological mediator of fibrotic diseases, enhanced miR-21 expression in primary pulmonary fibroblasts. Increasing miR-21 levels promoted, whereas knocking down miR-21 attenuated, the pro-fibrogenic activity of TGF-beta1 in fibroblasts. A potential mechanism for the role of miR-21 in fibrosis is through regulating the expression of an inhibitory Smad, Smad7. These experiments demonstrate an important role for miR-21 in fibrotic lung diseases and also suggest a novel approach using miRNA therapeutics in treating clinically refractory fibrotic diseases, such as IPF.

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  • There is ample evidence that miR-21 expression really is altered in many disease states.

    “One important point about all of these studies is that there is ample evidence that miR-21 expression really is altered in many disease states [11, 20, 77, 78].”

    From miR-21: a non‐specific biomarker of all maladies (2021) · cites this paper as [20]

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Cited by

Sorted by citations

Authors
Liu, G., Friggeri, A., Yang, Y., Milosevic, J., Ding, Q., Thannickal, V. J., Kaminski, N., & Abraham, E.
Affiliations
  • University of Alabama at Birmingham (US)
  • Dorothy P. and Richard P. Simmons Center for Interstitial Lung Diseases, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213 2
  • University of Pittsburgh (US)
Corresponding author
Liu, Gang
ORCID
Venue
Journal of Experimental Medicine
Publisher
Rockefeller University Press
Published
2010-07-19
Volume
207
Issue
8
Pages
1589-1597
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
DOI
10.1084/jem.20100035
PMC
PMC2916139
OpenAlex
W2159864284
Cited by
935
References
3
Citations by year
2026: 26 · 2025: 45 · 2024: 35 · 2023: 47 · 2022: 42 · 2021: 45 · 2020: 71 · 2019: 55 · 2018: 61 · 2017: 69 · 2016: 75 · 2015: 85 · 2014: 69 · 2013: 76 · 2012: 70
FWCI
56.01
Type
journal article
Language
en
Open access
Locations
  • The Journal of Experimental Medicine (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (R21HL097218, R01HL095397, R01HL067967, R01HL085324, R01HL076206)
  • National Institute of General Medical Sciences (R01GM087748, R01GM87748)
  • U.S. National Library of Medicine (R01LM009657)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Pulmonary Hypertension Research and Treatments
Keywords
miR-21, idiopathic pulmonary fibrosis, pulmonary fibrosis, lung fibroblasts, myofibroblasts, TGF-β1, Smad7, miRNA-based therapy, bleomycin-induced fibrosis, extracellular matrix synthesis
MeSH terms
Actins, Animals, Bleomycin, Cell Line, Collagen, Fibroblasts, Fibronectins, Humans, Lung, Mice, Inbred C57BL, Mice, Transgenic, Oligonucleotides, Phosphorylation, Pulmonary Fibrosis, Gene Expression, Extracellular Matrix Proteins, Antisense Elements (Genetics), MicroRNAs, Mice, Smad2 Protein, Smad7 Protein, Transforming Growth Factor beta1, Idiopathic Pulmonary Fibrosis

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