| First Author | Varisco BM | Year | 2012 |
| Journal | Am J Respir Cell Mol Biol | Volume | 46 |
| Issue | 6 | Pages | 765-72 |
| PubMed ID | 22268140 | Mgi Jnum | J:197892 |
| Mgi Id | MGI:5494831 | Doi | 10.1165/rcmb.2011-0316OC |
| Citation | Varisco BM, et al. (2012) Thy-1 signals through PPARgamma to promote lipofibroblast differentiation in the developing lung. Am J Respir Cell Mol Biol 46(6):765-72 |
| abstractText | 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-gamma (PPARgamma). 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 PPARgamma activity, and the inhibition or activation of PPARgamma reduced and increased triglyceride content, respectively. Thy-1 (-) fibroblasts were not responsive to either of the PPARgamma agonists ciglitazone or prostaglandin J(2), supporting the importance of Thy-1 in signaling via PPARgamma. 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 PPARgamma, 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. |
