190 Down-regulation of the NOTCH pathway during skin aging contributes to functional epidermal defects through miR-30a activation

Skin aging is a complex biological process leading to multiple functional defects in the different structure of skin tissues. Epidermal especially characterized by an alteration tissue renewal associated impairment keratinocytes differentiation process. We have previously reported that microRNA miR-30a over-expressed aged epidermis and we shown organotypic models this induction impairs epidermal differentiation, induces cell apoptosis, increases oxidative stress leads strong barrier function. MiR-30a appears therefore as key regulator aging. However, mechanisms modulating expression, during aging, need be clarified. hypothesized NOTCH signaling pathway could play role regulation since miR30a-MYC-NOTCH regulatory loop has been described cancer cells. To clarify human epidermis, used reporter system activity cultured treated chemical inhibitors. clearly observed activates expression keratinocytes, independently MYC expression. then investigated young vs samples skin. By immunofluorescence NOTCH1 receptor its intracellular part NICD, found significant inverse correlation between age patients Finally, identified putative binding site for transcriptional effector RBPJ promoter sequence miR-30a. Preliminary ChIP data indicates directly binds promoter. Altogether, our reveal contributes activation. These results open way potential strategies aiming at controlling