Hollborn Margrit, Bringmann Andreas, Faude Frank, Wiedemann Peter, Kohen Leon
Department of Ophthalmology and Eye Clinic, University of Leipzig Medical Faculty, 04103 Leipzig, Germany.
Biochem Biophys Res Commun. 2006 Jun 9;344(3):912-9. doi: 10.1016/j.bbrc.2006.03.185. Epub 2006 Apr 6.
We examined whether PDGF may directly stimulate the expression of VEGF by retinal pigment epithelial (RPE) cells in vitro, and the involvement of three signal transduction pathways in the regulation of PDGF-evoked cell proliferation, migration, and production of VEGF-A was investigated. PDGF stimulated the gene and protein expression of VEGF-A by RPE cells, and increased cell proliferation and chemotaxis. PDGF activated all signaling pathways investigated, as determined by increased phosphorylation levels of ERK1/2, p38, and Akt proteins. The three signaling pathways were involved in the mediation of PDGF-evoked cell proliferation, while p38 and PI3K mediated cell migration, and PI3K mediated secretion of VEGF-A. In addition to VEGF-A, the cells expressed mRNAs for various members of the VEGF family and for their receptors, including VEGF-B, -C, -D, flt-1, and KDR. The data indicate that PDGF selectively stimulates the expression of VEGF-A in RPE cells. PDGF evokes at least three signal transduction pathways which are differentially involved in various cellular responses.
我们研究了血小板衍生生长因子（PDGF）是否可在体外直接刺激视网膜色素上皮（RPE）细胞表达血管内皮生长因子（VEGF），并研究了三种信号转导途径在调节PDGF诱导的细胞增殖、迁移及VEGF-A产生中的作用。PDGF刺激RPE细胞中VEGF-A的基因和蛋白表达，并增加细胞增殖和趋化性。通过ERK1/2、p38和Akt蛋白磷酸化水平升高确定，PDGF激活了所有研究的信号通路。三种信号通路参与介导PDGF诱导的细胞增殖，而p38和磷脂酰肌醇-3-激酶（PI3K）介导细胞迁移，PI3K介导VEGF-A的分泌。除VEGF-A外，细胞还表达VEGF家族各成员及其受体的mRNA，包括VEGF-B、-C、-D、fms样酪氨酸激酶-1（flt-1）和激酶插入结构域受体（KDR）。数据表明，PDGF选择性刺激RPE细胞中VEGF-A的表达。PDGF引发至少三种信号转导途径，这些途径分别参与不同的细胞反应。
