TGF-BETA-1 INDUCES THE EXPRESSION OF TYPE-I COLLAGEN AND SPARC, AND ENHANCES CONTRACTION OF COLLAGEN GELS, BY FIBROBLASTS FROM YOUNG AND AGED DONORS

Fibroblasts have a major role in the synthesis and reorganization of e xtracellular matrix that occur during wound repair. An impaired biosyn thetic or functional response of these cells to stimulation by growth factors might contribute to the delayed wound healing noted in aging. We, therefore, compared the responses of dermal fibroblasts from young and elderly individuals (26, 29, 65, 89, 90, and 92 years of age) to transforming growth factor-beta1 (TGF-beta1) with respect to: (1) the synthesis of type I collagen and SPARC (two extracellular matrix prote ins that are highly expressed by dermal fibroblasts during the remodel ing phase of wound repair) and (2) the contraction of collagen gels, a n in vitro assay of wound contraction. With the exception of one young donor, all cultures exposed for 44 hours to 10 ng/ml TGF-beta1 exhibi ted a 1.6- to 5.5-fold increase in the levels of secreted type I colla gen and SPARC, relative to untreated cultures, and exhibited a 2.0- to 6.2-fold increase in the amounts of the corresponding mRNAs. Moreover , the dose-response to TGF-beta1 (0.1-10 ng/ml), as determined by synt hesis of type I collagen and SPARC mRNA, was as vigorous in cells from aged donors as in cells from a young donor. In assays of collagen gel contraction, fibroblasts from all donors were stimulated to a similar degree by 10 ng/ml TGF-beta1. In conclusion, cells from both young an d aged donors exhibited similar biosynthetic and contractile propertie s with exposure to TGF-beta1. It therefore appears that the impaired w ound healing noted in the aged does not result from a failure of their dermal fibroblasts to respond to this cytokine. (C) 1994 Wiley-Liss, Inc.