Diminished Response of Werner's Syndrome Fibroblasts to Growth Factors PDGF and FGF

• Published in: Science (American Association for the Advancement of Science) Vol. 234; no. 4781; pp. 1240 - 1243
• Main Authors: Bauer, Eugene A., Silverman, Neil, Busiek, Donald F., Kronberger, Annemarie, Deuel, Thomas F.
• Format: Journal Article
• Language: English
• Published: Washington, DC The American Association for the Advancement of Science 05.12.1986; American Association for the Advancement of Science
• Subjects: Adenomatosis, Familial endocrine; Biological and medical sciences; Blood; Cell Division - drug effects; Cell growth; Cultured cells; Dermatology; Disease; Dose-Response Relationship, Drug; Ethanol; Fibroblast growth factors; Fibroblast Growth Factors - pharmacology; Fibroblasts; Fibroblasts - drug effects; Genetics; Growth factors; Hereditary diseases of the skin. Congenital diseases of the skin. Haemangioma of the skin, of mucosae and of soft tissue; Heterozygotes; Humans; Medical research; Medical sciences; Messenger RNA; Microbial Collagenase - biosynthesis; Multiple endocrine neoplasia; Platelet-Derived Growth Factor - pharmacology; Receptors; Receptors, Cell Surface - metabolism; Receptors, Platelet-Derived Growth Factor; RNA, Messenger - biosynthesis; Ungulates; Werner syndrome; Werner Syndrome - metabolism; Cell culture; Fibroblast growth factor; Skin disease; Werner syndrome; Fibroblast; Platelet derived growth factor; Genetic disease
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.3022382

Patients with Werner's syndrome, an autosomal 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 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 skin 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 in Werner's syndrome cells may contribute to the phenotypic expression of the disorder.