UVB-induced TRPS1 regulates MITF transcription activity to promote skin pigmentation

• Published in: Biochimica et biophysica acta. Molecular basis of disease 2024-10, Vol.1870 (7), p.167445, Article 167445
• Main Authors: Zhang, Yushan, Hu, Yibo, Lei, Li, Jiang, Ling, Fu, Chuhan, Chen, Menglu, Wu, Songjiang, Duan, Xiaolei, Chen, Jing, Zeng, Qinghai
• Format: Article
• Language: English
• Subjects: Animals; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Gene Expression Regulation - radiation effects; Humans; Hyperpigmented dermatoses; Melanins - biosynthesis; Melanins - metabolism; Melanocytes - metabolism; Melanocytes - pathology; Melanocytes - radiation effects; Melanogenesis; Mice; Microphthalmia-Associated Transcription Factor - genetics; Microphthalmia-Associated Transcription Factor - metabolism; MITF; Promoter Regions, Genetic; Repressor Proteins - genetics; Repressor Proteins - metabolism; Skin - metabolism; Skin - pathology; Skin - radiation effects; Skin Pigmentation - genetics; Skin Pigmentation - radiation effects; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription, Genetic - radiation effects; TRPS1; Ultraviolet Rays - adverse effects; UVB
• ISSN: 0925-4439; 1879-260X; 1879-260X
• DOI: 10.1016/j.bbadis.2024.167445

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. [Display omitted] •UVB induces the expression of TRPS1 in human skin tissues and melanocytes.•TRPS1 can promote melanogenesis in pigment cells.•TRPS1 can promote melanogenesis by activating MITF transcriptional activity.