Document Detail

β-arrestin deficiency protects against pulmonary fibrosis in mice and prevents fibroblast invasion of extracellular matrix.
MedLine Citation:
PMID:  21411739     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Science translational medicine     Volume:  3     ISSN:  1946-6242     ISO Abbreviation:  Sci Transl Med     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-03-17     Completed Date:  2011-06-24     Revised Date:  2014-09-18    
Medline Journal Info:
Nlm Unique ID:  101505086     Medline TA:  Sci Transl Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  74ra23     Citation Subset:  IM    
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MeSH Terms
Antibiotics, Antineoplastic / adverse effects
Arrestins / deficiency*,  genetics
Bleomycin / adverse effects
Bronchoalveolar Lavage Fluid
Cell Adhesion
Cell Movement
Extracellular Matrix / metabolism,  pathology*
Fibroblasts / cytology,  metabolism
Idiopathic Pulmonary Fibrosis / chemically induced,  pathology*,  physiopathology*
Lung / metabolism,  pathology,  physiopathology
Mice, Inbred C57BL
Mice, Knockout
Transforming Growth Factor beta / metabolism
Grant Support
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/HL/NHLBI NIH HHS; R01 HL060539/HL/NHLBI NIH HHS; R01 HL060539-12/HL/NHLBI NIH HHS; R01 HL070631/HL/NHLBI NIH HHS; R01 HL077291/HL/NHLBI NIH HHS; R01 HL077291-07/HL/NHLBI NIH HHS; //Howard Hughes Medical Institute
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 0/Arrestins; 0/Transforming Growth Factor beta; 0/beta-arrestin; 11056-06-7/Bleomycin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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