werner@aecom.UUCP (Craig Werner) (12/07/86)
<> ! Diminshed Response of Werner's Syndrome Fibroblasts to ! Growth Factors PDGF and FGF ! Bauer EA, Silverman N, Busiek DF, Kronberger A, Deuel TF ! Science 234:1240 (5 Dec 1986) Patients with Werner's syndrome, an autosome recessive disorder, undergo an accelerated aging process that leads to premature death. Fibroblasts from such patients typically grow poorly in culture. Here it is shown that fibroblasts from a patient with Werner's syndrome have a markedly attenuated mitogenic response to a platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF). In contrast, they have a full mitogenic response to fetal bovine serum. Both PDGF binding and receptor numbers per cell are unaltered. The Werner's syndrome cells express high constitutive levels of collagenase in vitro. Although PDGF enhances collagenase expression through increased levels of hybridizable collagenase messenger RNA in normal shin fibroblasts, no induction of collagenase occurs in the Werner's syndrome fibroblasts. Moreover, the failure to respond to this agonist effect of PDGF is not restored by fetal bovine serum. The data suggest that failure of one or more PDGF-mediated pathways by Werner's syndrome cells may contribute to the phenotypic expression of the disorder. Note: Werner's Syndrome is an autosomal recessive disorder that is generally characterized by an apparent acceleration of many of the processes associated with aging. Some of the principal features, as defined by Thannhauser (*) are short stature with thin extremities and stocky trunk, premature graying of hair, premature baldness, patches of stiffened skin (especially in the face and lower extremities, trophic ulcers of the legs, juvenile cataracts, hypogonadism, tendency to diabetes, calcification of the blood vessels, osteoporosis, metastatic calcifications, and a tendency to occur in siblings. (*) SJ Thannhauser. Ann Int Med 23:559 (1945); Epstein, Martin, Schultz, Motulsky. Medicine 45:177 (1966); D Salk. Hum Genet 62:1 (1982). Other features include a thin high-pitched voice, an increased incidence of neoplasia, flat feet, hyperreflexia, and irregular dental development. -- Craig Werner (MD/PhD '91) !philabs!aecom!werner (1935-14E Eastchester Rd., Bronx NY 10461, 212-931-2517) "I wouldn't have invited me either."