Thömmes K B, Hoppe J, Vetter H, Sachinidis A
Medizinische Universitäts-Poliklinik, Wilhelmstr. 35-37, Bonn, 53111, Germany.
Exp Cell Res. 1996 Jul 10;226(1):59-66. doi: 10.1006/excr.1996.0202.
As previous studies showed, PDGF-AA exerts a poor mitogenic effect on vascular smooth muscle cells. Simultaneous addition of insulin-like growth factor 1 (IGF-1), itself also poorly mitogenic, led to a significant increase in [3H]thymidine incorporation into the cell DNA as well as a strong increase in cell number. To explain the synergistic effect of PDGF-AA and IGF-1 on VSMC proliferation, we describe the effects of the two growth factors on distinct intracellular signals: on the activation of the signal proteins mitogen-activated protein kinase (MAPK) isoforms p42 and p44 and on the protein kinase C (PKC) isoforms alpha, delta, and epsilon, and on the induction of the transcription factor c-fos. PDGF-AA strongly activated the MAPK isoforms and PKC delta as well as the induction of c-fos. In contrast, IGF-1 exerted no effect on the signals induced by PDGF-AA, but strongly activated PKC epsilon isoform. Comparing this signal pattern to the one of the mitogenically potent PDGF isoform PDGF-BB, we found that PDGF-BB activated all of the signal proteins investigated.
如先前研究所示，血小板衍生生长因子-AA（PDGF-AA）对血管平滑肌细胞的促有丝分裂作用较弱。同时添加胰岛素样生长因子1（IGF-1，其本身的促有丝分裂作用也较弱），导致[3H]胸苷掺入细胞DNA显著增加，细胞数量也大幅增加。为了解释PDGF-AA和IGF-1对血管平滑肌细胞增殖的协同作用，我们描述了这两种生长因子对不同细胞内信号的影响：对信号蛋白促分裂原活化蛋白激酶（MAPK）亚型p42和p44、蛋白激酶C（PKC）亚型α、δ和ε的激活，以及对转录因子c-fos的诱导。PDGF-AA强烈激活MAPK亚型、PKCδ以及c-fos的诱导。相比之下，IGF-1对PDGF-AA诱导的信号没有影响，但强烈激活PKCε亚型。将这种信号模式与促有丝分裂活性较强的PDGF亚型血小板衍生生长因子-BB（PDGF-BB）的信号模式进行比较，我们发现PDGF-BB激活了所有研究的信号蛋白。
