Caniggia I, Liu J, Han R, Buch S, Funa K, Tanswell K, Post M
Department of Paediatrics, Hospital for Sick Children Research Institute, Toronto, Canada.
Am J Respir Cell Mol Biol. 1993 Jul;9(1):54-63. doi: 10.1165/ajrcmb/9.1.54.
There is increasing evidence to suggest that platelet-derived growth factor (PDGF) or PDGF-like molecules play a role in fetal lung morphogenesis. Our previous studies demonstrated that fetal lung epithelial cells respond mitogenically to exogenous PDGF, while fetal lung fibroblasts respond with increased glycosaminoglycan synthesis. To further study the target cells of PDGF in fetal rat lung, we investigated the presence and nature of PDGF receptors in fetal lung cells. Functional PDGF receptors were expressed on normal epithelial cells of fetal rat lung. All three isoforms of PDGF (AA, AB, and BB) were mitogenic for quiescent epithelial cells. Northern blot and protein analysis demonstrated the presence of PDGF alpha-receptor and PDGF beta-receptor. All isoforms of PDGF enhanced tyrosine kinase activity and stimulated receptor autophosphorylation. In contrast, fetal lung fibroblasts expressed only the PDGF beta-receptor. PDGF-AB and PDGF-BB, but not PDGF-AA, stimulated tyrosine kinase activity. No PDGF isoform was mitogenic for quiescent fibroblasts. However, PDGF-BB stimulated fibroblast proliferation on a collagen type I substratum in the presence of transferrin. Binding experiments with [125I]PDGF-AA and [125I]-PDGF-BB to epithelial cells and fibroblasts confirmed these observations.
越来越多的证据表明，血小板衍生生长因子（PDGF）或PDGF样分子在胎儿肺形态发生中起作用。我们之前的研究表明，胎儿肺上皮细胞对外源性PDGF有促有丝分裂反应，而胎儿肺成纤维细胞则通过增加糖胺聚糖合成来做出反应。为了进一步研究PDGF在胎鼠肺中的靶细胞，我们调查了胎肺细胞中PDGF受体的存在情况和性质。功能性PDGF受体在胎鼠肺的正常上皮细胞上表达。PDGF的所有三种异构体（AA、AB和BB）对静止的上皮细胞都有促有丝分裂作用。Northern印迹和蛋白质分析证明了PDGFα受体和PDGFβ受体的存在。PDGF的所有异构体都增强了酪氨酸激酶活性并刺激了受体自身磷酸化。相比之下，胎儿肺成纤维细胞仅表达PDGFβ受体。PDGF-AB和PDGF-BB刺激酪氨酸激酶活性，但PDGF-AA不刺激。没有PDGF异构体对静止的成纤维细胞有促有丝分裂作用。然而，在转铁蛋白存在的情况下，PDGF-BB刺激了I型胶原基质上的成纤维细胞增殖。用[125I]PDGF-AA和[125I]-PDGF-BB与上皮细胞和成纤维细胞进行的结合实验证实了这些观察结果。
