Fig 3. KIT activation & up-regulation, concomitant parallel induction of ET3, KIT⁺Melan-A^–- progenitor cells, and melanocyte regeneration in proportion to sun-exposure.

(A), IHC of KIT and ET3 on serial sections of human skin specimen obtained from a lower extremity-amputation. Sole represents active suppression of melanogenesis (a and d), dorsum of big toe represents intermediate sun-exposure (b and e), and lateral lower leg represents heavy sun-exposure (c and f). (B), IHC of KIT, Melan-A, and ET3 on serial sections of human skin punch biopsy specimens obtained from sun-protected axilla (g, i, k) and chronic heavy sun-exposed forearm (h, j, l) from the same individual. Lymphocytes serve as internal negative control for KIT, ET3 and Melan-A; mast cells serve as internal positive control for KIT. Together, these images demonstrate that human skin exhibits sun-exposure-dependent up-regulation of KIT (a-c) and concomitant parallel sun-exposure-induced increasing induction of ET3 (d-f). Chronic sun-exposure induces intense dendritic pattern of KIT expression as well as a large increase in the number of KIT-expressing-cells in the basal layer (h) consisting of KIT⁺Melan-A⁺ mature melanocytes (j) and KIT⁺Melan-A^–melanocyte progenitor cells as evidenced by the difference between (h) and (j).