School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, China; College of Pharmacy and Research Institute for Drug Development, Chonnam National University, Gwangju, Republic of Korea; School of Life Science, Huzhou University, Huzhou, China.
College of Pharmacy and Research Institute for Drug Development, Chonnam National University, Gwangju, Republic of Korea.
J Invest Dermatol. 2023 Jan;143(1):26-36.e8. doi: 10.1016/j.jid.2022.07.009. Epub 2022 Aug 6.
Skin photoaging is a complicated pathological process and is mainly due to UV irradiation, especially UVB irradiation. Damage induction by UVB is a complex process, involving intricate molecular mechanisms. The formation of bulky photoproducts in the DNA globally affects transcription and splicing and results in the dysfunction of keratinocytes. In this study, we show that δ-catenin is predominantly distributed in keratinocytes of the skin epidermis and functionally accelerates cell proliferation and DNA repair. Ex vivo protein profiling reveals that δ-catenin upregulates the phosphorylation of RSK2 by enhancing the interaction between PDK1 and RSK2 and thereby induces the nuclear accumulation of YB1 to promote proliferation and DNA repair. Moreover, δ-catenin overexpression induces in vivo keratinocyte proliferation and DNA repair in UVB-irradiated mouse skin. Notably, acidic fibroblast GF/FGFR1 is identified as one of the key upstream signalings of δ-catenin by inducing δ-catenin stabilization. The involvement of δ-catenin in keratinocyte proliferation and DNA repair may suggest δ-catenin as a target for the treatment of UVB damage.
皮肤光老化是一个复杂的病理过程，主要是由于紫外线照射，特别是 UVB 照射。UVB 诱导的损伤是一个复杂的过程，涉及复杂的分子机制。DNA 中大量光产物的形成会全局影响转录和剪接，导致角质形成细胞功能障碍。在这项研究中，我们表明 δ-连环蛋白主要分布在皮肤表皮的角质形成细胞中，并通过加速细胞增殖和 DNA 修复发挥功能。体外蛋白质谱分析表明，δ-连环蛋白通过增强 PDK1 和 RSK2 之间的相互作用，上调 RSK2 的磷酸化，从而诱导 YB1 的核积累，促进增殖和 DNA 修复。此外，δ-连环蛋白过表达可诱导 UVB 照射的小鼠皮肤中角质形成细胞的增殖和 DNA 修复。值得注意的是，酸性成纤维细胞生长因子/FGFR1 通过诱导 δ-连环蛋白的稳定被鉴定为 δ-连环蛋白的一个关键上游信号之一。δ-连环蛋白在角质形成细胞增殖和 DNA 修复中的参与表明，δ-连环蛋白可能是治疗 UVB 损伤的一个靶点。
