Caniggia I, Post M
Department of Paediatrics, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.
Am J Physiol. 1992 Oct;263(4 Pt 1):L495-500. doi: 10.1152/ajplung.1992.263.4.L495.
Lung morphogenesis is in part regulated by extracellular matrix (ECM), and cytokines may indirectly control lung development via modulation of ECM. In the present study, we investigated the effect of different platelet-derived growth factor (PDGF) isoforms AA, AB, and BB on the synthesis of glycosaminoglycans (GAG) by fetal rat lung cells. Independent of gestational age, PDGF-BB, but not PDGF-AA or -AB, stimulated GAG synthesis of fetal lung fibroblasts. In contrast, GAG synthesis by epithelial cells was not affected by any of the PDGF molecules. The stimulatory effect of PDGF-BB on fibroblast GAG biosynthesis was dose (> 10 ng/ml) and time (> 8 h) dependent. The relative proportion of the individual GAG molecules was not altered by PDGF-BB exposure. Blockage of tyrosine kinase activity with staurosporine did abolish the effect of PDGF-BB on fibroblast GAG formation. Actinomycin D and cycloheximide did not abrogate the PDGF-BB effect, suggesting that no new RNA or protein synthesis is required. The proteoglycan synthesis blocker, beta-D-xyloside, also did not inhibit the PDGF-BB action on fibroblast GAG synthesis. These data suggest that the effect of PDGF on GAG synthesis is cell type and isoform specific and is most likely a direct effect on the GAG chain elongation enzymes.
肺形态发生部分受细胞外基质（ECM）调控，细胞因子可能通过调节ECM间接控制肺发育。在本研究中，我们调查了不同血小板衍生生长因子（PDGF）亚型AA、AB和BB对胎鼠肺细胞糖胺聚糖（GAG）合成的影响。与胎龄无关，PDGF-BB而非PDGF-AA或-AB刺激胎肺成纤维细胞的GAG合成。相反，上皮细胞的GAG合成不受任何PDGF分子影响。PDGF-BB对成纤维细胞GAG生物合成的刺激作用具有剂量（>10 ng/ml）和时间（>8小时）依赖性。PDGF-BB处理未改变各GAG分子的相对比例。用星形孢菌素阻断酪氨酸激酶活性确实消除了PDGF-BB对成纤维细胞GAG形成的作用。放线菌素D和环己酰亚胺并未消除PDGF-BB的作用，这表明不需要新的RNA或蛋白质合成。蛋白聚糖合成阻滞剂β-D-木糖苷也未抑制PDGF-BB对成纤维细胞GAG合成的作用。这些数据表明，PDGF对GAG合成的作用具有细胞类型和亚型特异性，很可能是对GAG链延长酶的直接作用。
