The long-term goal of this research is to determine the molecular mechanism(s) whereby ultraviolet radiation (UVR)-induced cell injury regulates the human ornithine decarboxylase gene in skin and how agents such as retinoic acid modulate the cellular response to UVR-induced cell injury. This project will lead to a mechanistic understanding of how ultraviolet radiation and retinoid combined therapy improves psoriasis and allow us to test better retinoids and phototherapies to better treat psoriasis.
SPECIFIC AIMS : (1) To define the effect of ultraviolet B (UVB) on the ornithine decarboxylase enzyme activity in cultured human keratinocytes. (2) To determine whether the levels of ODC mRNA are increased in parallel with the UVB-induced increase in ODC enzyme activity. (3) To determine whether the increased level of ODC mRNA is the result of increased stability of the mRNA or whether it represents increased transcription of the ODC gene. (4) To examine the promoter of the human ODC gene to define which regions are necessary for UVB-induction of ODC gene transcription. (5) To evaluate the effect of retinoic acid on UVB induction of the ODC gene.
