Thy-1 signals through PPARγ to promote lipofibroblast differentiation in the developing lung.
Thy-1 signals through PPARγ to promote lipofibroblast differentiation in the developing lung.
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DOI：
10.1165/rcmb.2011-0316oc
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发表时间：
2012-12
影响因子：
6.4
通讯作者：
B. Varisco;N. Ambalavanan;J. Whitsett;J. Hagood
中科院分区：
文献类型：
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作者：
B. Varisco;N. Ambalavanan;J. Whitsett;J. Hagood
Thy - 1是一种糖基磷脂酰肌醇连接的细胞表面糖蛋白，存在于一部分肺成纤维细胞上，在出生后的肺泡形成过程中起重要作用。在本研究中，我们明确了Thy - 1在肺脂肪成纤维细胞分化以及通过过氧化物酶体增殖物激活受体 - γ（PPARγ）调节脂质稳态中的作用。在体内，Thy - 1与含有脂滴的间质细胞相关。将Thy - 1转染到Thy - 1（ - ）成纤维细胞中会增加甘油三酯含量、脂肪酸摄取以及脂肪成纤维细胞标记物脂肪细胞分化相关蛋白的表达。Thy - 1（ + ）成纤维细胞表现出高2.4倍的PPARγ活性，并且PPARγ的抑制或激活分别降低和增加了甘油三酯含量。Thy - 1（ - ）成纤维细胞对PPARγ激动剂环格列酮或前列腺素J₂均无反应，这支持了Thy - 1在通过PPARγ信号传导中的重要性。Thy - 1（ + ）成纤维细胞表达的脂肪酸转运蛋白 - 3 mRNA浓度显著更高，并且表现出更高的脂肪酸摄取率和增加的甘油三酯含量。抑制脂肪酸转运蛋白功能会降低Thy - 1（ + ）成纤维细胞的脂质含量。在新生期，C57BL / 6肺成纤维细胞中Thy - 1的表达增加，这与肺泡形成的开始时间一致。Thy - 1通过PPARγ的表达促进脂肪成纤维细胞分化，通过脂肪酸酯化刺激脂质积累，并增强由脂肪酸转运蛋白介导的脂肪酸摄取。Thy - 1在发育中的肺的脂肪成纤维细胞分化调节中很重要。
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.