Effects of Ultraviolet A and B Irradiation on the Transcriptional Regulation of Stromelysin-1 Gene in Human Fibroblast Cultures

Abstract

Background: Sun exposure and therapeutic irradiation have been shown to induce alterations in extracellular matrix (ECM) proteins, including elastin, glycosaminoglycan and collagens. The integrity of the connective tissue mainly depends on balanced rates of matrix synthesis and degradation of the extracellular matrix. Therefore, matrix metalloproteinases (MMPs) may be involved in ultraviolet irradiation (UVR)-induced alterations in ECM proteins. Objective: To evaluate the effects of UVA as well as UVB irradiations on ST-1 gene expression in cultured human skin fibroblasts. Methods: After exposure of different doses of UVA and UVB on cultured human skin fibroblasts, we examined the expression of ST-1 gene by Northern blot analysis, chloramphenicol acetyltransferase (CAT) assay with CAT construct containing AP-1 binding site.Additionally, we carried out the gel mobility shift assay to investigate the effects of UVR on the DNA-binding activity of AP-1 Results: After UVR on fibroblasts, the steady-state levels of ST-1 mRNA were increased in response to UVA and UVB by 2.5-fold and 4.2-fold, respectively, as compared with controls. Similar results were obtained by CAT assay showing that CAT activity increased as the UVA and UVB doses increased. Furthermore, gel mobility shift assay demonstrated that both UVA and UVB increased AP-1 DNA binding complexes. Conclusion: UVB as well as UVA up-regulated ST-1 gene expression at transcriptional levels in vitro. We speculate that modulation of MMPs, including ST-1, gene expression by UVR may contribute to the connective tissue damage related to photoaging and other photocutaneous disorders. (Ann Dermatol 11(4) 225~231,1999).