Department of Medical Science, School of Medicine, Walailak University, Nakhon Si Thammarat 80160, Thailand.
Research Center in Tropical Pathobiology, Walailak University, Nakhon Si Thammarat 80161, Thailand.
Cells. 2024 Oct 8;13(19):1661. doi: 10.3390/cells13191661.
The skin microenvironment created by keratinocytes (KC) influences the stress responses of melanocytes (MC) to UVB insults. This study employed RNA sequencing analysis as well as in vitro and in vivo models to elucidate the underlying mechanisms. Our RNA-Seq analysis revealed a statistically significant upregulation of GCSF and CCL20 genes in UVB-irradiated KC, correlating with the protective effects of KC on MC responses to UVB exposure. Recombinant GCSF and CCL20 exhibited the most pronounced modulation of UVB-induced MC responses. These effects included the attenuation of apoptosis and reduction of ROS formation, along with the upregulation of tyrosinase and tyrosinase-related protein-1, which are involved in the melanogenic pathway. ELISA was also used to confirm that UVB could induce the secretion of GCSF and CCL20 from KC. A similar correlation between GCSF and CCL20 expression in KC and tyrosinase levels in MC was observed in UVB-irradiated mouse skin. Our study provides novel insights into the protective role of GCSF and CCL20 in the paracrine effects of KC on UVB-induced MC damage through the modulation of stress response pathways, the MITF-tyrosinase axis, and the regulation of p53. These findings have implications for the development of pharmacological strategies targeting KC-derived paracrine factors for the prevention of skin photodamage.
角质形成细胞 (KC) 创造的皮肤微环境会影响黑素细胞 (MC) 对 UVB 损伤的应激反应。本研究采用 RNA 测序分析以及体外和体内模型来阐明潜在机制。我们的 RNA-Seq 分析表明，UVB 照射的 KC 中 GCSF 和 CCL20 基因的表达显著上调，这与 KC 对 MC 对 UVB 暴露的反应的保护作用相关。重组 GCSF 和 CCL20 对 UVB 诱导的 MC 反应表现出最显著的调节作用。这些作用包括抑制凋亡和减少 ROS 形成，以及上调参与黑色素生成途径的酪氨酸酶和酪氨酸酶相关蛋白-1。ELISA 还用于证实 UVB 可以诱导 KC 分泌 GCSF 和 CCL20。在 UVB 照射的小鼠皮肤中，KC 中的 GCSF 和 CCL20 表达与 MC 中的酪氨酸酶水平之间也观察到类似的相关性。本研究通过调节应激反应途径、MITF-酪氨酸酶轴和 p53 调节，提供了角质形成细胞对 UVB 诱导的 MC 损伤的旁分泌作用中 GCSF 和 CCL20 的保护作用的新见解。这些发现对于开发针对 KC 衍生旁分泌因子的药理学策略以预防皮肤光损伤具有重要意义。
