Premium
Altered regulation of platelet‐derived growth factor A‐chain and c‐fos gene expression in senescent progeria fibroblasts
Author(s) -
Winkles Jeffrey A.,
O'Connor Mary L.,
Friesel Robert
Publication year - 1990
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041440218
Subject(s) - progeria , microbiology and biotechnology , growth factor , gene expression , gene , biology , c fos , genetics , receptor
The study of human genetic disorders known as premature aging syndromes may provide insight into the mechanisms of cellular senescence. These diseases are clinically characterized by the premature onset and accelerated progression of numerous features normally associated with human aging. Previous studies have indicated that fibroblasts derived from premature aging syndrome patients have in vitro growth properties similar to senescent fibroblasts from normal individuals. As an initial approach to determine whether gene expression is altered in premature aging syndrome fibroblasts, RNA was prepared from various cell strains and used for gel blot hybridization experiments. Although normal fibroblasts only express platelet‐derived growth factor (PDGF) A‐chain mRNA for a brief period following mitogenic stimulation, one strain of Hutchinson‐Gilford (progeria) syndrome fibroblasts, AG3513, consdtutively expresses PDGF A‐chain mRNA and PDGF‐AA homodimers. The PDGF A‐chain gene does not appear to be amplified or rearranged in these fibroblasts. AG3513 progeria fibroblasts have properties characteristic of senescent cells, including an altered morphology and a diminished mitogenic response to growth promoters. The diminished response of AG3513 progeria fibroblasts to PDGF stimulation was examined in some detail. Studies using 125 I‐PDGF‐BB, which binds with high affinity to both A‐ and B‐type PDGF receptors, indicate that normal and AG3513 progeria fibroblasts have a similar number of PDGF receptors. Although receptor autophosphorylation occurs normally in PDGF‐stimulated AG3513 progeria fibroblasts, c‐fos mRNA induction does not. The senescent phenotype of AG3513 fibroblasts is probably unrelated to their constitutive PDGF A‐chain gene expression; further studies are necessary in order to directly address this issue. Also, additional analysis of this progeria fibroblast strain may provide information on the control of mitogeninducible gene expression in normal cells.