Karlsson C, Paulsson Y
Department of Pathology, University Hospital, Uppsala, Sweden.
J Cell Physiol. 1994 Feb;158(2):256-62. doi: 10.1002/jcp.1041580207.
We have previously found that stimulation of normal neonatal fibroblasts with PDGF or EGF leads to a transient induction of PDGF A-chain mRNA and the synthesis of PDGF-AA proteins. This finding may imply the existence of an autocrine feedback mechanism to amplify the mitogenic signal under certain conditions. We have now studied the PDGF-BB mediated PDGF A-chain induction in a set of fibroblasts from young and old donors to clarify if the levels of induction are correlated to the donor age and the replicative capacity of the cells. The PDGF A-chain induction was found to be reduced in cells from old donors compared with cells from embryonic and neonatal donors. The different cell strains were also characterized further with respect to PDGF receptor expression and PDGF binding properties. PDGF beta-receptors were found to be enhanced in old donor cell strains, whereas the PDGF alpha-receptors showed more variability in expression between the strains. The PDGF A-chain mRNA induction was also decreased or absent in late passage human fibroblasts (senescent cells) when compared with early passage cells. These data suggest that the PDGF A-chain mRNA induction is regulated by an age related mechanism in human fibroblasts.
我们之前发现，用血小板衍生生长因子（PDGF）或表皮生长因子（EGF）刺激正常新生成纤维细胞会导致PDGF A链mRNA的短暂诱导以及PDGF-AA蛋白的合成。这一发现可能意味着存在一种自分泌反馈机制，在某些条件下放大有丝分裂信号。我们现在研究了PDGF-BB介导的一组来自年轻和年老供体的成纤维细胞中PDGF A链的诱导情况，以阐明诱导水平是否与供体年龄和细胞的复制能力相关。结果发现，与来自胚胎和新生供体的细胞相比，来自老年供体的细胞中PDGF A链的诱导减少。还进一步对不同细胞株的PDGF受体表达和PDGF结合特性进行了表征。发现老年供体细胞株中的PDGFβ受体增强，而PDGFα受体在各细胞株之间的表达变化更大。与早期传代细胞相比，晚期传代的人成纤维细胞（衰老细胞）中PDGF A链mRNA的诱导也减少或不存在。这些数据表明，人成纤维细胞中PDGF A链mRNA的诱导受年龄相关机制的调节。
