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, Oct 10, 2015
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    • " studies have shown that alterations in Wnt secretion and consequent modulation of intracellular signaling interferes with the lipid metabolism at PPARc level . The Wnt4 - induced reduction in PPARc levels seems especially important as PPARc and its down - stream target , ADRP are responsible for the uptake of triglycerides from the blood stream ( Varisco et al . , 2012 ) that is essential for surfactant production in ATII cells . Our data have also shown that PPARc is necessary in epithelial cells to regulate surfactant production . As surfactant lining of the alveoli is essential to uniform inflation and to protect against chemical or particulate injury of the distal lungs , a decrease in surfactant "
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    • "Pulmonary fibroblasts were isolated from PND14 mice by previously described methods which yield >85% fibroblast purity [30,31]. Briefly, PND14 mice were sacrificed and their lungs inflated by gently instilling dispase (BD Biosciences) via the trachea and then plugging the trachea with 1% low melting point agarose. "
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    • "To characterize the CD166 pos lung stromal cell subset (Fig. 2A), we assessed the incidence of clonal cells using the CFU-F assay, and determined their potential for lipofibroblastic and myofibroblastic differentiation in the presence of BMP-4 and TGF-β respectively. Lung lipofibroblast differentiation was assessed by the staining of lipid droplets with Oil-Red O (Varisco et al., 2012). Myofibroblast differentiation was assessed by the expression of alpha smooth muscle actin (α-SMA), a component of stress fibers that confers contractile properties to myofibroblasts (Hinz et al., 2007, 2012). "
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