109 Short and repeated climatic changes affect the epidermal differentiation program and lead to matrix remodeling in a human organotypic skin model

Our skin needs constantly to get used to various changes of its environment. Ambient temperature and hygrometry represent key parameters of climatic conditions that can be suddenly modified. Very sparse data are available to date concerning the molecular response of human skin to repeated climate changes. To go further into this question, we used a versatile model of skin equivalent (SE) composed of a porous polymer populated by human fibroblasts on top of which were further seeded human keratinocytes. During the epidermal differentiation, repeated daily “hot/wet” (40°C and 80% RH) or “cold/dry” (10°C and 40% RH) climatic stresses were applied on these SEs. After 45 days of culture, the samples were collected for RNA extraction and histological preparation. To obtain an exhaustive view of the molecular mechanisms elicited by climate changes, we performed large-scale gene expression analysis by DNA microarrays and looked for modulated function by bio-informatic annotation. This analysis revealed several functions, including epidermal differentiation and extra-cellular matrix, impacted by repeated variations in climatic conditions. Some of these molecular changes were confirmed by histological examination and protein expression. Both treatments reduced the expression of genes encoding collagens, laminin and proteoglycans, suggesting a profound remodeling of the extracellular matrix. We also observed a strong induction of the entire family of LCE genes after cold/dry exposure that was confirmed at the protein level. These changes were correlated with an increase of epidermal differentiation markers and a thickening of the stratum corneum, indicating a possible implementation of defense mechanisms against dehydration. Our study reveals for the first time the complex pattern of molecular response allowing human skin adaption to repeated changes of its climatic environment.