Regulations of collagen synthesis by ascorbic acid, transforming growth factor-beta and interferon-gamma in human dermal fibroblasts cultured in three-dimensional collagen gel are photoaging- and aging-independent

Abstract

Decreased collagen synthesis and loss of responsiveness to growth factors are well known phenomena in in vivo or in vitro aged cells. Ascorbic acid and some cytokines such as transforming growth factor-beta and interferon-gamma are important regulators of collagen synthesis. To investigate the responsiveness of fibroblasts with regard to the photoaging and aging process, we examined the effect of ascorbic acid, TGF-beta, and IFN-gamma on collagen synthesis in dermal fibroblasts from three newborn foreskins (1 day old) and in both exposed and unexposed skin fibroblasts from 4 old individuals (60-76 years old) cultured in monolayer and in collagen gel. We demonstrated that basal levels of collagen synthesis decreased with increasing age. Photoaged fibroblasts in collagen gel showed greater basal collagen synthesis than aged fibroblasts in the same individuals, but similar basal collagen synthesis in monolayer cultures. Even though basal levels of collagen synthesis in collagen gel are downregulated in a photoaging- and aging-dependent manner, collagen synthesis by ascorbic acid in collagen gel, and by TGF-beta and IFN-gamma in both monolayer culture and collagen gel were regulated in a photoaging- and aging-independent manner. In monolayer culture, however, the responsiveness to ascorbic acid in newborn fibroblasts was greater than in photoaged and aged fibroblasts. Our results suggest that there are differences in collagen synthesis between photoaged and aged cells, depending on culture conditions. Responsiveness to ascorbic acid, TGF-beta and IFN-gamma related to collagen synthesis in photoaged and aged fibroblasts in collagen gel appears to be the same as in newborn fibroblasts, even though basal levels of collagen synthesis are downregulated in a photoaging- or aging-dependent manner.