FAMILIAL CO-SEGREGATION OF THE ELASTIN PHENOTYPE IN SKIN FIBROBLASTS FROM HUTCHINSON-GILFORD PROGERIA

Elastin and type IV collagen production are markedly elevated in fibro blasts derived from the skin of patients with Hutchinson-Gilford proge ria (HGP). Fibroblasts from three affected children and their parents were compared to normal human skin fibroblasts with respect to elastin production as a function of different concentrations of calf serum an d the cytokines, transforming growth factor-beta and basic fibroblast growth factor (TGF-beta1, bFGF). In cultured fibroblasts from the pare nts of probands that were very high elastin producers (> 10(5) Molecul ar equivalents/cell per h), at least one parent (mother) presented the same phenotype. Overproduction of elastin in culture could have been due to increased sensitivity of HGP strains to stimuli present in seru m; however, relative stimulation of elastin production by calf serum i n cell strains from HGP elastin over-producers was less than half the control strain. In most of the cultures examined, the responsiveness o f elastin production to TGF-beta1 was almost absent when compared to t he response of normal fibroblasts. HGP strains with high elastin produ ction modified conditioned medium to enhance elastin production in nor mal cells. These results suggest the presence, in HGP skin fibroblasts , of inheritance of high elastin production that is associated with ac celerated aging.