Reduced expression of mRNA for transforming growth factor beta (TGF beta) and TGF beta receptors I and II and decreased TGF beta binding to the receptors in in vitro-aged fibroblasts.
Previous studies have demonstrated that the expression of type I collagen, the most abundant protein in the dermis, is reduced in in vitro-aging fibroblast cultures, but the mechanism controlling the reduction of type I collagen expression is not understood. Recent studies, however, have demonstrated that transforming growth factor beta (TGF beta) plays an important role in the regulation of type I collagen expression. The purpose of this study was to investigate the role of TGF beta in downregulation of type I collagen expression in in vitro-aged fibroblasts. 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 mRNA levels of alpha 1(I) collagen, TGF beta, and TGF beta receptors I and II in late-passage fibroblasts were reduced to 62%, 62%, 59% and 59%, respectively, of those in early-passage fibroblasts. We also compared TGF beta receptor binding in early- and late-passage fibroblasts using receptor binding assays. The affinity of 125I-TGF beta in late-passage fibroblasts was lower than that in early-passage fibroblasts. These results suggest that the reduction of type I collagen expression in in vitro-aged fibroblasts is regulated by reduced expression of TGF beta and TGF beta receptors I and II and by decreased TGF beta receptor binding ability of the fibroblasts.
Mori
Y
Y
Department of Dermatology, Kawasaki Medical School, Kurashiki, Japan.
Hatamochi
A
A
Arakawa
M
M
Ueki
H
H
D030201:Activin Receptors, Type I; D000328:Adult; D016922:Cellular Senescence; D003094:Collagen / Q000235:genetics; D017364:Collagenases / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D008297:Male; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism*; D012867:Skin / Q000166:cytology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism*
D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D003094:Collagen; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D017364:Collagenases