Association of p63 with Proliferative Potential in Normal and Neoplastic Human Keratinocytes

p63, a recently identified member of the p53 gene family, encodes multiple products with transactivating, death-inducing, and dominant-negative activities. We show that in normal human epidermis, in hair follicles, and in stratified epidermal cultures, p63 protein is principally restricted to cells with high proliferative potential and is absent from the cells that are undergoing terminal differentiation. In normal human epidermis and in hair follicles, basal cells with abundant p63 are interspersed with cells with little or no p63. Whenever p63 mRNA is present, it encodes mainly truncated, potentially dominant-negative isotypes. In squamous cell carcinomas, the number of cells containing p63 and their distribution depends on the degree of anaplasia. In highly differentiated tumors, p63 is confined to a ring of basal-like cells surrounding, but at a distance from, centers of terminal differentiation. In less differentiated tumors, most cells contain p63 and their distribution is chaotic with respect to centers of terminal differentiation. p63 appears to be a valuable diagnostic marker for anaplastic keratinocytes

Biological effects of air pollution on the function of human skin equivalents

Abstract The World Health Organization reports that 99% of the global population are exposed to pollution levels higher than the recommended air quality guidelines. Pollution‐induced changes in the skin have begun to surface; however, the effects require further investigation so that effective protective strategies can be developed. This study aimed to investigate some of the aging‐associated effects caused by ozone and particulate matter (PM) on human skin equivalents. Full‐thickness skin equivalents were exposed to 0.01 μg/μL PM, 0.05 μg/μL PM, 0.3 ppm ozone, or a combination of 0.01 μg/μL PM and 0.3 ppm ozone, before skin equivalents and culture medium were harvested for histological/immunohistochemical staining, gene and protein expression analysis using qPCR, Western blotting, and ELISA. Markers include MMP‐1, MMP‐3, COL1A1, collagen‐I, 4‐HNE, HMGCR, and PGE2. PM was observed to induce a decrease in epidermal thickness and an enhanced matrix building phenotype, with increases in COL1A1 and an increase in collagen‐I protein expression. By contrast, ozone induced an increase in epidermal thickness and was found to induce a matrix‐degrading phenotype, with decreases in collagen‐I gene/protein expression and increases in MMP‐1 and MMP‐3 gene/protein expression. Ozone was also found to induce changes in lipid homeostasis and inflammation induction. Some synergistic damage was also observed when combining ozone and 0.01 μg/μL PM. The results presented in this study identify distinct pollutant‐induced effects and show how pollutants may act synergistically to augment damage; given individuals are rarely only exposed to one pollutant type, exposure to multiple pollutant types should be considered to develop effective protective interventions