Transforming growth factor-beta antagonizes alveolar type II cell proliferation induced by keratinocyte growth factor.
Transforming growth factor-beta antagonizes alveolar type II cell proliferation induced by keratinocyte growth factor.
复制标题
转化生长因子-β 拮抗角化细胞生长因子诱导的肺泡 II 型细胞增殖。
DOI：
10.1165/rcmb.2004-0182oc
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发表时间：
2004
影响因子：
6.4
通讯作者：
Mason,RobertJ
中科院分区：
文献类型：
--
作者：
Zhang,Feijie;Nielsen,LarryD;Lucas,JosephJ;Mason,RobertJ
Keratinocyte growth factor (KGF) is a mitogen for rat type II cells and also stimulates differentiationin vitro. Administration of KGF also protects the lung from a variety of injuries and subsequent development of fibrosis. Because transforming growth factor (TGF)-β has been shown to inhibit epithelial cell proliferation and surfactant protein gene expression in other systems and is thought to be a major effector in pulmonary fibrosis, we sought to determine if TGF-β would antagonize the effects of KGF in primary cultures of alveolar type II cells. Type II cells were cultured on a matrix of type I collagen and Matrigel in the presence or absence of KGF and/or TGF-β. KGF alone greatly stimulated proliferation and increased cyclin-dependent kinase (cdk) 2 kinase activity and Retinoblastoma susceptibility gene product (Rb) phosphorylation. Cyclin D1, cdk2, and cdc25A protein levels were increased, and p15Ink4band p27Kip1protein levels were decreased. TGF-β markedly inhibited alveolar epithelial cell proliferation induced by KGF. TGF-β inhibited cdk2 enzyme activity and Rb phosphorylation and increased p15Ink4bprotein levels. TGF-β also inhibited differentiation induced by KGF as measured by secretion of surfactant protein–A into the apical media. In summary, TGF-β inhibits the proliferative effect of KGFin vitroand may be a biologic antagonist of KGF.
