Modulation of Gene Expression Induced in Human Epidermis by Environmental Stress In Vivo

Environmental insults on the skin induce biologic responses through the modulation of expression of genes implicated in different cell functions. The aim of this study was to investigate the modulation of gene expression profile in human epidermis in vivo following different stresses. We determined the modulations of gene expression using cDNA macroarray in the epidermis of 28 healthy volunteers, following mild and physiologic insults, including: (1), tape stripping; (2) application of 10% sodium dodecyl sulfate; (3) daily application of vaseline; and (4), exposure to one minimal erythema dose of solar-simulated radiation. The analysis was performed 19 h after treatment. The reverse transcription–polymerase chain reaction method was used to confirm our results. We showed that: (1) the intensity of gene modulation was variable among the volunteers following the same skin stress; (2) the nature and intensity of skin treatment modified the pattern of gene expression; and (3) some genes were modulated only by specific stress, some others are modulated irrespective of the stress. GADD45, Bax, SAS, and granulocyte chemotactic protein-2 were overexpressed exclusively following solar-simulated radiation, whereas tape stripping led to the modulation of genes implicated in different pathways (inflammation, cell proliferation, cell differentiation, detoxification, etc.). Concerning common gene modulation, MRP8 and MRP14 were highly upregulated in human skin epidermis after solar-simulated radiation, vaseline application or tape stripping, and to a lower extent after sodium dodecyl sulfate. Such upregulation of the MRP 8/14 genes was confirmed at the protein level in an ex-vivo skin culture model following tape stripping and solar-simulated radiation. Together, these results suggest that MRP8 and MRP14 may be general, yet highly sensitive, markers for a great variety of skin stresses and that they are implicated in several epidermal repair pathways