werner@aecom.UUCP (Craig Werner) (12/07/86)
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! 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."