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Science 5 December 1986:
Vol. 234. no. 4781, pp. 1240 - 1243
DOI: 10.1126/science.3022382

Articles

Science, Vol 234, Issue 4781, 1240-1243
Copyright © 1986 by American Association for the Advancement of Science


articles

Diminished response of Werner's syndrome fibroblasts to growth factors PDGF and FGF

EA Bauer, N Silverman, DF Busiek, A Kronberger, and TF Deuel

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.


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Down-regulation of Akt/PKB in senescent cardiac fibroblasts impairs PDGF-induced cell proliferation.
C. Diez, M. Nestler, U. Friedrich, M. Vieth, M. Stolte, K. Hu, J. Hoppe, and A. Simm (2001)
Cardiovasc Res 49, 731-740
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Dissociation of Oct-1 from the Nuclear Peripheral Structure Induces the Cellular Aging-associated Collagenase Gene Expression.
S.-i. Imai, S. Nishibayashi, K. Takao, M. Tomifuji, T. Fujino, M. Hasegawa, and T. Takano (1997)
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Werner's Syndrome: Evidence for Preferential Regional Expression of a Generalized Mesenchymal Cell Defect.
E. A. Bauer, J. Uitto, E. M. L. Tan, and K. A. Holbrook (1988)
Arch Dermatol 124, 90-101
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