Long-Lasting Molecular Changes in Human Skin after Repetitive in situ UV Irradiation

摘要

It is known that UV modulates the expression of paracrine factors that regulate melanocyte function in the skin. We have investigated the consequences of repetitive UV exposure of human skin in biopsies of 10 subjects with phototypes 2-3.5 taken 1-4 yr later. The expression of melanogenic factors (TYR, MART1, MITF), growth factors/receptors (SCF/KIT, bFGF/FGFR1, ET1/EDNRB, HGF, GM-CSF), adhesion molecules (β-catenin, E-cadherin, N-cadherin), cell cycle proteins (PCNA, cyclins D1, E2) as well as Bcl-2, DKK1 and DKK3, were analyzed by immunohistochemistry. Most of those markers showed no detectable changes at ≥1 yr after the repetitive UV irradiation. While increased expression of EDNRB protein was detected in 3 of 10 UV-irradiated subjects, there was no detectable change in the expression of ET1 protein or in EDNRB mRNA levels. In summary, only the expression of TYR, MART1 and/or EDNRB, and only in some subjects, was elevated at ≥1 yr post-UV irradiation. Thus the long-term effects of repetitive UV irradiation on human skin did not lead to significant changes in skin morphology and there is considerable subject-to-subject variation in responses. The possibility that changes in the expression and function of EDNRB triggers downstream activation of abnormal melanocyte proliferation and differentiation deserves further investigation.