Department of Dermatology, The Third Xiangya Hospital, Central South University, Changsha, China.
Clinical Research Center, The Second Xiangya Hospital, Central South University, Changsha, China.
Biochim Biophys Acta Mol Basis Dis. 2024 Oct;1870(7):167445. doi: 10.1016/j.bbadis.2024.167445. Epub 2024 Jul 27.
Hyperpigmented dermatoses are characterized by increased skin pigmentation caused by genetic, environmental factors and inflammation, which lasts a long time and is difficult to treat. Ultraviolet (UV), especially ultraviolet B (UVB), is the primary external factor inducing skin pigmentation. However, the specific regulatory mechanisms are not fully understood. Through analysis of GEO datasets from four UV-exposed skin cell/tissue samples, we found that TRPS1 is the only gene differentially expressed in multiple datasets (GSE22083, GSE67098 and GSE70280) and highly positively correlated with the expression of key melanogenesis genes. Consistently, we observed that TRPS1 is highly expressed in sun-exposed skin tissues compared to non-exposed skin. Additionally, the expression of TRPS1 was also significantly upregulated after UVB irradiation in isolated skin tissues and melanocytes, while knockdown of TRPS1 expression inhibited the UVB-induced melanogenesis. Further research revealed that overexpression of TRPS1 increased melanin content and tyrosinase activity in MNT1 cells, as well as upregulated the expression levels of key melanogenesis genes (MITF, TYR, TYRP1, DCT). In contrast, inhibition of TRPS1 expression showed the opposite effect. Moreover, we found that TRPS1 can bind to the promoter region of MITF, inhibiting the expression of MITF can antagonize the melanogenesis induced by TRPS1. In conclusion, UVB-induced TRPS1 promotes melanogenesis by activating the transcriptional activity of MITF.
色素沉着性皮肤病的特征是由于遗传、环境因素和炎症导致的皮肤色素沉着增加,这种情况持续时间长,且难以治疗。紫外线(UV),尤其是中波紫外线(UVB),是诱导皮肤色素沉着的主要外部因素。然而,具体的调节机制尚不完全清楚。通过对四个暴露于 UV 的皮肤细胞/组织样本的 GEO 数据集进行分析,我们发现 TRPS1 是多个数据集(GSE22083、GSE67098 和 GSE70280)中唯一差异表达的基因,且与关键黑色素生成基因的表达高度正相关。一致地,我们观察到 TRPS1 在暴露于阳光的皮肤组织中的表达明显高于非暴露的皮肤。此外,TRPS1 的表达在离体皮肤组织和黑素细胞中经 UVB 照射后也显著上调,而 TRPS1 表达的敲低则抑制了 UVB 诱导的黑色素生成。进一步的研究表明,TRPS1 的过表达增加了 MNT1 细胞中的黑色素含量和酪氨酸酶活性,以及上调了关键黑色素生成基因(MITF、TYR、TYRP1、DCT)的表达水平。相反,抑制 TRPS1 的表达则显示出相反的效果。此外,我们发现 TRPS1 可以结合到 MITF 的启动子区域,抑制 MITF 的表达可以拮抗 TRPS1 诱导的黑色素生成。总之,UVB 诱导的 TRPS1 通过激活 MITF 的转录活性来促进黑色素生成。