Decreased expression of the platelet-derived growth factor beta-receptor in fibroblasts from a patient with Werner's syndrome.

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.