期刊
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
卷 46, 期 6, 页码 765-772出版社
AMER THORACIC SOC
DOI: 10.1165/rcmb.2011-0316OC
关键词
Thy-1; lipofibroblast; PPAR gamma; lipid metabolism
资金
- Dixon Foundation (through Children's Health Systems, Birmingham, Alabama)
- Kaul Pediatric Research Initiative (through Children's Health Systems, Birmingham, Alabama)
- National Institutes of Health [R01-HL082818, R01-HL92906]
- American Thoracic Society Fellow Career Development Grant [F-09-035]
- Translational Research in Normal and Disordered Development Program of the University of Alabama at Birmingham
- Research Facilities Improvement Program Grant from the National Center for Research Resources [C06RR 15,490]
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 (PPAR gamma). 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 PPAR gamma activity, and the inhibition or activation of PPAR gamma reduced and increased triglyceride content, respectively. Thy-1 (-) fibroblasts were not responsive to either of the PPAR gamma agonists ciglitazone or prostaglandin J(2), supporting the importance of Thy-1 in signaling via PPAR gamma. 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 PPAR gamma, 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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