Paracrine crosstalk between endothelial cells and melanocytes through clusterin to inhibit pigmentation

Cutaneous vasculature systems play a role in regulating skin pigmentation. We analysed RNA sequencing data to identify novel antimelanogenic factors secreted from endothelial cells and found that one of the secreted factors, clusterin, is highly expressed by HDMECs. To investigate the paracrine effect of clusterin from HDMECs on the regulation of melanogenesis, HDMECs were infected with clusterin or sh‐clusterin lentivirus and the HDMEC‐derived conditioned media were used to treat normal human melanocytes. It was found that HDMEC‐derived clusterin inhibits melanogenesis through MITF/tyrosinase downregulation. The findings here suggest that HDMECs secrete copious amounts of clusterin and that the clusterin is a factor contributing to the inhibitory effect of endothelial cells on melanogenesis via paracrine crosstalk between endothelial cells and melanocytes.