Mori S, Kawano M, Kanzaki T, Morisaki N, Saito Y, Yoshida S
Department of Internal Medicine, School of Medicine, Chiba University, Japan.
Eur J Clin Invest. 1993 Mar;23(3):161-5. doi: 10.1111/j.1365-2362.1993.tb00755.x.
The study of Werner's syndrome, a premature ageing syndrome, may provide insight into the processes of natural ageing. We investigated the reason for the reduced growth potential of fibroblasts in Werner's syndrome which is considered to be similar to that of fibroblasts in normal senescence. The responses to different isoforms of platelet-derived growth factor (PDGF) of fibroblasts from a patient with Werner's syndrome (W-cells) and from a normal subject (control cells) were assessed by [3H]thymidine incorporation assay, a 125I-PDGF-AB binding experiment, and Northern blot analysis with a PDGF beta-receptor specific cDNA probe. PDGF-stimulated increase in [3H]thymidine incorporation in W-cells was much lower than that in control cells, especially with PDGF-AB and -BB as mitogens. The specific binding of 125I-PDGF-AB to W-cells was correspondingly lower than that to control cells. Furthermore, Northern blot analysis demonstrated a decreased basal level, and lack of PDGF-AB-induced up-regulation of the PDGF beta-receptor transcript in W-cells. Decreased expression of the PDGF beta-receptor due to decrease in its synthesis may be a causative factor of the decreased mitogenic response of W-cells to PDGF.
对早老综合征——沃纳综合征的研究，可能有助于深入了解自然衰老的过程。我们研究了沃纳综合征中成纤维细胞生长潜力降低的原因，该综合征被认为与正常衰老过程中的成纤维细胞类似。通过[3H]胸苷掺入试验、125I-PDGF-AB结合实验以及用PDGFβ受体特异性cDNA探针进行的Northern印迹分析，评估了一名沃纳综合征患者的成纤维细胞（W细胞）和一名正常受试者的成纤维细胞（对照细胞）对不同亚型血小板衍生生长因子（PDGF）的反应。PDGF刺激后，W细胞中[3H]胸苷掺入的增加远低于对照细胞，尤其是以PDGF-AB和-BB作为促细胞分裂剂时。125I-PDGF-AB与W细胞的特异性结合相应低于与对照细胞的结合。此外，Northern印迹分析表明，W细胞中PDGFβ受体转录本的基础水平降低，且缺乏PDGF-AB诱导的上调。由于PDGFβ受体合成减少导致其表达降低，可能是W细胞对PDGF促有丝分裂反应降低的一个致病因素。
