University Bordeaux, Inserm, BRIC, Bordeaux, France.
Department of Dermatology and Pediatric Dermatology, National Reference Centre for Rare Disorders, Hôpital des Enfants Pellegrin, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.
Dev Growth Differ. 2023 May;65(4):194-202. doi: 10.1111/dgd.12848. Epub 2023 Mar 18.
Ultraviolet B (UVB) in sunlight cause skin damage, ranging from wrinkles to photoaging and skin cancer. UVB can affect genomic DNA by creating cyclobutane pyrimidine dimers (CPDs) and pyrimidine-pyrimidine (6-4) photoproducts (6-4PPs). These lesions are mainly repaired by the nucleotide excision repair (NER) system and by photolyase enzymes that are activated by blue light. Our main goal was to validate the use of Xenopus laevis as an in vivo model system for investigating the impact of UVB on skin physiology. The mRNA expression levels of xpc and six other genes of the NER system and CPD/6-4PP photolyases were found at all stages of embryonic development and in all adult tissues tested. When examining Xenopus embryos at different time points after UVB irradiation, we observed a gradual decrease in CPD levels and an increased number of apoptotic cells, together with an epidermal thickening and an increased dendricity of melanocytes. We observed a quick removal of CPDs when embryos are exposed to blue light versus in the dark, confirming the efficient activation of photolyases. A decrease in the number of apoptotic cells and an accelerated return to normal proliferation rate was noted in blue light-exposed embryos compared with their control counterparts. Overall, a gradual decrease in CPD levels, detection of apoptotic cells, thickening of epidermis, and increased dendricity of melanocytes, emulate human skin responses to UVB and support Xenopus as an appropriate and alternative model for such studies.
阳光中的紫外线 B（UVB）会导致皮肤损伤，范围从皱纹到光老化和皮肤癌。UVB 可以通过产生环丁烷嘧啶二聚体（CPDs）和嘧啶-嘧啶（6-4）光产物（6-4PPs）来影响基因组 DNA。这些损伤主要通过核苷酸切除修复（NER）系统和蓝光激活的光解酶来修复。我们的主要目标是验证非洲爪蟾（Xenopus laevis）作为研究 UVB 对皮肤生理学影响的体内模型系统的有效性。在胚胎发育的所有阶段和所有测试的成年组织中，都发现了 xpc 和 NER 系统的其他六个基因以及 CPD/6-4PP 光解酶的 mRNA 表达水平。当在 UVB 照射后不同时间点检查非洲爪蟾胚胎时，我们观察到 CPD 水平逐渐降低，凋亡细胞数量增加，同时表皮增厚，黑色素细胞树突增多。与在黑暗中相比，当胚胎暴露在蓝光下时，我们观察到 CPD 的快速清除，证实了光解酶的有效激活。与对照胚胎相比，暴露在蓝光下的胚胎中凋亡细胞数量减少，增殖速度加快恢复正常。总的来说，CPD 水平逐渐降低、检测到凋亡细胞、表皮增厚和黑色素细胞树突增多，模拟了人类皮肤对 UVB 的反应，支持非洲爪蟾作为此类研究的合适替代模型。
