Evaluation of peroxisome proliferator-activated receptor beta/delta (PPAR beta/delta) behavior in skin regeneration processes and its modulation by ligands

Abstract

The Peroxisome Proliferator-activated Receptor beta/delta (PPAR beta/delta) is a transcription factor, member of the nuclear receptor's superfamily. This protein can be found in several human tissues, mainly in tissues involved in high lipid metabolism and dependents on cell proliferation and differentiation, such as skin, intestine, placenta, adipose tissue, brain and skeletal muscle. PPAR beta/delta heterodimerizes with the Retinoid X Receptor (RXR). On ligand's presence, the heterodimer can activate some gene transcription through coactivator recruitment into promoter region. A gene which expression is regulated by PPAR beta/delta is the cytokine Transforming Growth Factor ²1 (TGF ²1) gene. This cytokine can regulate the expression of some proteins important in maintaining skin structure, such as type I collagen, matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). The unbalance on collagen, MMPs and TIMPs production is one of the factors that prompt the skin aging and wrinkling, due to structural disorganization that this unbalance cause in the tissue. Previous studies showed the PPAR beta/delta role on skin regeneration, collagen production and stratum corneum revitalization. With this in mind, this study aims the identification of compounds (natural or synthetic) that may act as PPAR beta/delta agonist or antagonist, with anti-aging role. In this project, we will study how PPAR beta/delta behaves in tissue regeneration, after its modulation by ligands, through cell approach and in vitro protein characterization. (AU)