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

Abstract

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.

Regulation of Human Skin Pigmentation in situ by Repetitive UV Exposure: Molecular Characterization of Responses to UVA and/or UVB

“…In contrast, UVA seems to elicit no similar increase in any melanogenesis-related factors. IPD and PPD have been known for some time to reflect the relatively rapid oxidative effects of UVA on preexisting melanin and melanin intermediates in the skin (as discussed in (Brenner et al , 2009; Coelho et al , 2009)). IPD and PPD typically appear relatively quickly and then disappear within a short time thereafter.…”

Heat stress: A risk factor for skin carcinogenesis

“…CPDs and 6-4PPs are formed as a result of a photochemical reaction between UVB and the DNA, leading to covalent linkage of adjacent thymine dimers (Figure 1.2), inducing significant changes in the nucleotide structure (Besarutinia et al, 2004;Yogianti et al, 2012). CPD formation generally occurs at sites of methylated cytosines, and thus an abundance of methylated cytosines in a particular DNA region increases susceptibility to UV radiation-induced damage at these sites (Aigal et al, 2015;Brenner et al, 2009). Thus, CpG islands, DNA regions containing 5-methylcytosines, are hotspots for such DNA mutations (Ikehata et al, 2003;Ikehata and Ono, 2011).…”

Grundlagen der Hautpigmentierung

“…Neben den Melanozyten werden auch Keratinozyten und Fibroblasten durch UVStrahlung zur Expression melanogener Faktoren, insbesondere Wachstumsfaktoren, angeregt [3,4]. Hormone spielen ebenfalls eine wichtige Rolle für die Regulierung der Hautpigmentierung.…”