miR-21 mediates fibrogenic activation of pulmonary fibroblasts and lung fibrosis
| Autor: | Victor J. Thannickal, Edward Abraham, Naftali Kaminski, Yanping Yang, Jadranka Milosevic, Gang Liu, Qiang Ding, Arnaud Friggeri |
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| Rok vydání: | 2010 |
| Předmět: |
Pathology
Pulmonary Fibrosis Oligonucleotides Gene Expression Smad2 Protein SMAD Extracellular matrix Mice chemistry.chemical_compound Idiopathic pulmonary fibrosis 0302 clinical medicine Fibrosis Pulmonary fibrosis Immunology and Allergy Phosphorylation Lung Extracellular Matrix Proteins 0303 health sciences respiratory system 3. Good health medicine.anatomical_structure 030220 oncology & carcinogenesis Collagen Myofibroblast medicine.medical_specialty Immunology Mice Transgenic Biology Bleomycin Cell Line Smad7 Protein Transforming Growth Factor beta1 03 medical and health sciences medicine Animals Humans 030304 developmental biology Brief Definitive Report Cell Biology Fibroblasts medicine.disease Actins Idiopathic Pulmonary Fibrosis Fibronectins respiratory tract diseases Mice Inbred C57BL MicroRNAs Antisense Elements (Genetics) chemistry |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| Popis: | 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-β1, 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-β1 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. |
| Databáze: | OpenAIRE |
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