표피와 모낭에서 CRTC3 결핍 시 멜라닌 세포 분화 억제에 관한 연구

Abstract

The mechanisms that lead to variation in human skin and hair color are not fully understood and melanocyte system is the most important strategy against environmental hazards. To better understand the molecular control of skin and hair color variation and tanning response (as a tool of environmental prevention response) to cAMP stimuli (UVR), we knocked out modulation of the expression of CRTC3 (CREB-regulated transcriptional co-activator 3), CREB coactivator in mice. Depletion of CRTC3 was sufficient to lighten the color of the mouse hair and tail (ear) skin in Knock-out (K/O). Ultra-structural studies revealed that depletion of CRTC3 inhibited the accumulation of both early and mature melanosomes while melanin contents and early and late melanogenesis-associated genes were much reduced in hairy dorsal skin and tail skin. Knock-down (K/D) of CRTC3 in mel-ab cells and primary cultured cells from the mice showed consistent results with those of in vivo and cAMP tended to recover the downregulation of melanogenesis genes. These results indicated that CRTC3 is a determinant of color of skin and hair both ways of facultative (basal) and stimulated state of adapted melanogenesis. CRTC3 contributes to melanogenesis by modulating CRTC3/MITF.