Reduced expression of mRNA for transforming growth factor β(TGFβ) and TGFβ receptors I and II and decreased TGFβ binding to the receptors in in vitro-aged fibroblasts

Abstract

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.

Effect of the abrogation of TGF-β1 by antisense oligonucleotides on the expression of TGF-β-isoforms and their receptors I and II in isolated fibroblasts from keloid scars

“…These findings suggest a regulation between TGF-ß1 and its receptors. There is growing evidence for a regulatory mechanism between TGF-ß1 and TGF-ßRI and TGF-ßRII in an autocrine fashion (3,34). Bock et al theorized that cytokines alone do not induce fibrosis, but it is more likely that a certain combination of TGFs and their receptors may lead to increased ECM synthesis.…”

Characteristics and Pathomechanisms of Endogenously Aged Skin

“…In parallel, there is an observed reduction in the expression of tissue inhibitors of metalloproteinases [14, 77, 78]. Another common feature is the increased insoluble degraded collagen and the reduction of type I and III procollagen synthesis, which may result from the impaired TGFβ signalling pathway [77, 79]. …”

A Single Arm, Monocentric, Prospective, Open Label Study to Evaluate Anti-Ageing Efficacy of Human Growth Factors and Cytokines Containing Cosmetic Skin Serum in Indian Female Population

“…The subjective assessments corroborated with dermatological Natural extension of this application of therapy using conditioned medium is the treatment of aging. It is known that endogenous growth factors reduce with age [11]. Hence, administration of growth factors makes it logical for treatment of skin aging.…”