Genome-Wide RNA Sequencing Analysis in Human Dermal Fibroblasts Exposed to Low-Dose Ultraviolet A Radiation

• Published in: Genes Vol. 13; no. 6; p. 974
• Main Authors: Wang, Jinyun, Yano, Satoshi, Xie, Kun, Ohata, Yoshihisa, Hara, Taichi
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 29.05.2022; MDPI
• Subjects: Aging; Apoptosis; Biomarkers; Cell growth; DNA damage; Electron transport; Epidermis; Erythema; Fibroblasts; Gene expression; Gene regulation; Genes; Genetic aspects; Genomes; Health aspects; Insulin; Medical research; Medicine, Experimental; p53 Protein; Phenotypes; Proteins; Radiation; Ribonucleic acid; Risk factors; RNA; RNA sequencing; Senescence; Sequence analysis; Skin; Skin diseases; Thermal cycling; Tumor suppressor genes; Tumors; Ultraviolet radiation; Japan; United States > US
• ISSN: 2073-4425; 2073-4425
• DOI: 10.3390/genes13060974

Ultraviolet A (UVA) radiation can pass through the epidermis and reach the dermal skin layer, contributing to photoaging, DNA damage, and photocarcinogenesis in dermal fibroblasts. High-dose UVA exposure induces erythema, whereas low-dose, long-term UVA exposure causes skin damage and cell senescence. Biomarkers for evaluating damage caused by low-dose UVA in fibroblasts are lacking, making it difficult to develop therapeutic agents for skin aging and aging-associated diseases. We performed RNA-sequencing to investigate gene and pathway alterations in low-dose UVA-irradiated human skin-derived NB1RGB primary fibroblasts. Differentially expressed genes were identified and subjected to Gene Ontology and reactome pathway analysis, which revealed enrichment in genes in the senescence-associated secretory phenotype, apoptosis, respiratory electron transport, and transcriptional regulation by tumor suppressor p53 pathways. Insulin-like growth factor binding protein 7 (IGFBP7) showed the lowest p-value in RNA-sequencing analysis and was associated with the senescence-associated secretory phenotype. Protein–protein interaction analysis revealed that Fos proto-oncogene had a high-confidence network with IGFBP7 as transcription factor of the IGFBP7 gene among SASP hit genes, which were validated using RT-qPCR. Because of their high sensitivity to low-dose UVA radiation, Fos and IGFBP7 show potential as biomarkers for evaluating the effect of low-dose UVA radiation on dermal fibroblasts.