Thy-1 Signals through PPARγ to Promote Lipofibroblast Differentiation in the Developing Lung

Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH 45229, USA.
American Journal of Respiratory Cell and Molecular Biology (Impact Factor: 3.99). 01/2012; 46(6):765-72. DOI: 10.1165/rcmb.2011-0316OC
Source: PubMed


Thy-1 is a glycosylphosphytidylinositol-linked cell-surface glycoprotein present on a subset of lung fibroblasts, which plays 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. The 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. Thy-1 (+) fibroblasts exhibited 2.4-fold higher PPARγ activity, and the 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), supporting the importance of Thy-1 in signaling via PPARγ. Thy-1 (+) fibroblasts expressed significantly higher concentrations of fatty-acid transporter protein-3 mRNA, and demonstrated higher rates of fatty-acid uptake and increased triglyceride content. The inhibition of fatty-acid transporter protein function reduced Thy-1 (+) fibroblast lipid content. The expression of Thy-1 in C57BL/6 lung fibroblasts increased during the neonatal period, coinciding with the onset of alveolarization. Thy-1 promoted lipofibroblast differentiation via the expression of PPARγ, stimulated lipid accumulation via fatty-acid esterification, and enhanced the fatty-acid uptake mediated by fatty-acid transporter proteins. Thy-1 is important in the regulation of lipofibroblast differentiation in the developing lung.

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Available from: Brian M Varisco,
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    • "Thy-1 also independently plays a role in alveolar formation (Nicola et al. 2009). One means by which Thy-1 maintains a lipogenic fibroblast phenotype is by stimulating peroxisome proliferator activated receptor gamma (PPAR) signaling and PPAR directed transcription of lipid enhancing genes (Varisco et al. 2012). Hypermethylation of the Thy-1 promoter silences Thy 1, producing myofibroblast differentiation. "
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