REGULATION OF MELANOGENESIS BY THE AMINO-ACID TRANSPORTER SLC7A5.

Abstract Integration of ChIPseq and microarray data allowed to identify to our knowledge previously unreported MITF target genes, among which, the amino acid transporter, SLC7A5. We showed that siRNA-mediated SLC7A5 knock-down decreased pigmentation in B16F10 cells, without affecting morphology nor dendricity. Treatment with the SLC7A5 inhibitors BCH, or JPH203, also decreased melanin synthesis in B16F10 cells. Our findings indicated that BCH was as potent as reference depigmenting agent, Kojic Acid, but acted through a different pathway not affecting tyrosinase activity. BCH also decreased pigmentation in human MNT1 melanoma cells or normal human melanocytes. Finally, we tested BCH on a more physiological model, using reconstructed human epidermis and confirmed a strong inhibition of pigmentation demonstrating the clinical potential of SLC7A5 inhibition and positioning BCH as a depigmenting agent suitable for cosmetic or dermatologic intervention in hyperpigmentation diseases.