| β-arrestin deficiency protects against pulmonary fibrosis in mice and prevents fibroblast invasion of extracellular matrix. | |
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MedLine Citation:
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PMID: 21411739 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Idiopathic pulmonary fibrosis is a progressive disease that causes unremitting extracellular matrix deposition with resulting distortion of pulmonary architecture and impaired gas exchange. β-Arrestins regulate G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptors through receptor desensitization while also acting as signaling scaffolds to facilitate numerous effector pathways. Here, we examine the role of β-arrestin1 and β-arrestin2 in the pathobiology of pulmonary fibrosis. In the bleomycin-induced mouse lung fibrosis model, loss of either β-arrestin1 or β-arrestin2 resulted in protection from mortality, inhibition of matrix deposition, and protected lung function. Fibrosis was prevented despite preserved recruitment of inflammatory cells and fibroblast chemotaxis. However, isolated lung fibroblasts from bleomycin-treated β-arrestin-null mice failed to invade extracellular matrix and displayed altered expression of genes involved in matrix production and degradation. Furthermore, knockdown of β-arrestin2 in fibroblasts from patients with idiopathic pulmonary fibrosis attenuated the invasive phenotype. These data implicate β-arrestins as mediators of fibroblast invasion and the development of pulmonary fibrosis, and as a potential target for therapeutic intervention in patients with idiopathic pulmonary fibrosis. |
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Authors:
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Alysia Kern Lovgren; Jeffrey J Kovacs; Ting Xie; Erin N Potts; Yuejuan Li; W Michael Foster; Jiurong Liang; Eric B Meltzer; Dianhua Jiang; Robert J Lefkowitz; Paul W Noble |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Science translational medicine Volume: 3 ISSN: 1946-6242 ISO Abbreviation: Sci Transl Med Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-03-17 Completed Date: 2011-06-24 Revised Date: 2012-05-31 |
Medline Journal Info:
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Nlm Unique ID: 101505086 Medline TA: Sci Transl Med Country: United States |
Other Details:
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Languages: eng Pagination: 74ra23 Citation Subset: IM |
Affiliation:
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Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antibiotics, Antineoplastic / adverse effects Arrestins / deficiency*, genetics Bleomycin / adverse effects Bronchoalveolar Lavage Fluid Cell Adhesion Cell Movement Extracellular Matrix / metabolism, pathology* Fibroblasts / cytology, metabolism Humans Idiopathic Pulmonary Fibrosis / chemically induced, pathology*, physiopathology* Lung / metabolism, pathology, physiopathology Mice Mice, Inbred C57BL Mice, Knockout Transforming Growth Factor beta / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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HL016347/HL/NHLBI NIH HHS; HL060539/HL/NHLBI NIH HHS; HL077291/HL/NHLBI NIH HHS; HL16037/HL/NHLBI NIH HHS; HL70631/HL/NHLBI NIH HHS; R01 HL016037-39/HL/NHLBI NIH HHS; R01 HL060539/HL/NHLBI NIH HHS; R01 HL060539-12/HL/NHLBI NIH HHS; R01 HL070631-09/HL/NHLBI NIH HHS; R01 HL077291-06A1/HL/NHLBI NIH HHS; R01 HL077291-07/HL/NHLBI NIH HHS; R01 HL077291-08/HL/NHLBI NIH HHS; //Howard Hughes Medical Institute |
| Chemical | |
Reg. No./Substance:
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0/Antibiotics, Antineoplastic; 0/Arrestins; 0/Transforming Growth Factor beta; 0/beta-arrestin; 11056-06-7/Bleomycin |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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