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Thy-1 Signals through PPARγ to Promote Lipofibroblast Differentiation in the Developing Lung.
MedLine Citation:
PMID:  22268140     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Thy-1 is a glycosylphosphytidylinositol linked cell surface glycoprotein present on a subset of lung fibroblasts that has an important role in postnatal alveolarization. In the present study, we define the role of Thy-1 in pulmonary lipofibroblast differentiation and in the regulation of lipid homeostasis via Peroxisome Proliferator-Activated Receptor-γ (PPARγ). Thy-1 was associated with interstitial cells containing lipid droplets in vivo. Transfection of Thy-1 into Thy-1 (-) fibroblasts increased triglyceride content, fatty acid uptake, and the expression of the lipofibroblast marker adipocyte differentiation related protein (ADRP). Thy-1 (+) fibroblasts exhibited 2.4 fold higher PPARγ activity, and inhibition or activation of PPARγ reduced and increased triglyceride content, respectively. Thy-1 (-) fibroblasts were not responsive to either of the PPARγ agonists ciglitazone or Prostaglandin J(2) (PGJ(2)) supporting the importance of Thy-1 in signaling via PPARγ. Thy-1 (+) fibroblasts expressed significantly higher levels of fatty acid transporter protein 3 mRNA, had higher rates of fatty acid uptake and increased triglyceride content. Inhibition of fatty acid transporter protein function reduced Thy-1 (+) fibroblast lipid content. Expression of Thy-1 in C57BL/6 lung fibroblasts increased in the neonatal period, coinciding with the onset of alveolarization. Thy-1 promoted lipofibroblast differentiation via expression of PPARγ, stimulated lipid accumulation via fatty acid esterification, and enhanced fatty acid uptake mediated by fatty acid transporter proteins. Thy-1 is important in the regulation of lipofibroblast differentiation and function in the developing lung.
Authors:
Brian M Varisco; Namasivayam Ambalavanan; Jeffrey A Whitsett; James S Hagood
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-20
Journal Detail:
Title:  American journal of respiratory cell and molecular biology     Volume:  -     ISSN:  1535-4989     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8917225     Medline TA:  Am J Respir Cell Mol Biol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Cincinnati Children's Hospital Research Foundation, Cincinnati, Ohio, United States.
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