Pertovaara L, Kaipainen A, Mustonen T, Orpana A, Ferrara N, Saksela O, Alitalo K
Department of Pathology, University of Helsinki, Finland.
J Biol Chem. 1994 Mar 4;269(9):6271-4.
Transforming growth factor beta (TGF-beta) is a multifunctional polypeptide that regulates the proliferation and differentiation of various cells and has an angiogenic effect in vivo, although it inhibits the growth of cultured endothelial cells. We report here that TGF-beta treatment of quiescent cultures of mouse embryo-derived AKR-2B cells, which are growth-stimulated by TGF-beta, and human lung adenocarcinoma A549 cells, which are growth-inhibited by TGF-beta, results in the induction of vascular endothelial growth factor (VEGF) mRNA and protein. Maximal VEGF mRNA levels occurred 4-8 h after stimulation with a decline to background levels in 24 h. In contrast, the related placenta growth factor mRNA was not induced by TGF-beta in these cells. No VEGF receptor mRNA was seen in AKR-2B cells. Also, TGF-beta treatment of endothelial cells, which express the FLT1 and KDR/FLK-1 receptors for VEGF, did not cause VEGF induction. Because VEGF is known to be a strong angiogenic factor for endothelial cells, the results suggest that the angiogenic effect of TGF-beta on endothelial cells in blood vessels may be mediated at least partly by a paracrine induction of VEGF in other surrounding cell types.
转化生长因子β（TGF-β）是一种多功能多肽，可调节多种细胞的增殖和分化，在体内具有血管生成作用，尽管它会抑制培养的内皮细胞生长。我们在此报告，用TGF-β处理静止培养的小鼠胚胎来源的AKR-2B细胞（这些细胞受TGF-β刺激生长）和人肺腺癌A549细胞（这些细胞受TGF-β抑制生长），会导致血管内皮生长因子（VEGF）mRNA和蛋白的诱导。刺激后4-8小时出现最大VEGF mRNA水平，24小时后降至背景水平。相比之下，相关的胎盘生长因子mRNA在这些细胞中未被TGF-β诱导。在AKR-2B细胞中未检测到VEGF受体mRNA。此外，用TGF-β处理表达VEGF的FLT1和KDR/FLK-1受体的内皮细胞，不会导致VEGF的诱导。由于VEGF已知是内皮细胞的一种强大血管生成因子，结果表明TGF-β对血管内皮细胞的血管生成作用可能至少部分是由其他周围细胞类型中VEGF的旁分泌诱导介导的。
