Inhibition of ultraviolet radiation mediated extracellular matrix remodeling in fibroblasts by transforming growth factor-beta

摘要

The extracellular matrix is synthesized predominantly by fibroblasts and gives tissue its structural integrity. It is remodeled by ultraviolet radiation via the increased expression/activities of matrixmetalloproteinases (MMP) and inhibition of the tissue inhibitors of matrix metalloproteinases (TIMP). On the other hand, transforming growth factor-beta (TGF-beta) stimulates extracellular matrix deposition. The hypothesis of the research was the counteraction of UV radiation effects on fibroblasts by a TGF-P inducing agent (AT). Non-irradiated and UVB radiated fibroblasts were exposed to AT and examined for MMP-1 promoter activity, and expression of MMP-2, TIMP-1, and TIMP-2. AT inhibited MMP-1 promoter activity and dramatically stimulated MMP-2 expression; its effects were antagonized by UV radiation. The dramatic stimulation of TIMPs by AT predominated in non-irradiated and UV irradiated fibroblasts. TGF-beta induction in fibroblasts is therefore an effective strategy to counteract UV radiation induced damage to the extracellular matrix, particularly through the induction of TIMPs.