REDUCED EXPRESSION OF MESSENGER-RNA FOR TRANSFORMING-GROWTH-FACTOR-BETA (TGF-BETA) AND TGF-BETA RECEPTOR-I AND RECEPTOR-II AND DECREASED TGF-BETA BINDING TO THE RECEPTORS IN IN VITRO-AGED FIBROBLASTS

Previous studies have demonstrated that the expression of type I colla gen, the most abundant protein in the dermis, is reduced in in vitro-a ging fibroblast cultures, but the mechanism controlling the reduction of type I collagen expression is not understood, Recent studies, howev er, hare demonstrated that transforming growth factor beta (TGF beta) plays an important role in the regulation of type I collagen expressio n, The purpose of this study was to investigate the role of TGF beta i n downregulation of type I collagen expression in in vitro-aged fibrob lasts, We compared the expression of mRNA for alpha 1(I) collagen, TGF beta, TGF beta type I receptor and TGF beta type II receptor in early - and late-passage fibroblasts by Northern blot hybridizations, The mR NA levels of alpha 1(I) collagen, TGF beta, and TGF beta receptors I a nd II in late-passage fibroblasts were reduced to 62%, 62%, 59% and 59 %, respectively, of those in early-passage fibroblasts. We also compar ed TGF beta receptor binding in early- and late-passage fibroblasts us ing receptor binding assays, The affinity of I-125-TGF beta in late-pa ssage fibroblasts was lower than that in early-passage fibroblasts, Th ese results suggest that the reduction of type I collagen expression i n in vitro-aged fibroblasts is regulated by reduced expression of TGF beta and TGF beta receptors I and II and by decreased TGF beta recepto r binding ability of the fibroblasts.