Combined Transcriptomic and Proteomic Analyses Reveal the Different Responses to UVA and UVB Radiation in Human Keratinocytes

Abstract

Ultraviolet (UV) radiation from sunlight is a major risk factor for many cutaneous pathologies including skin aging and cancers. Despite decades of research, the different responses to UVA and UVB in human keratinocytes have not been systemically investigated. Here, we performed multi-omics to characterize the common and different changes in gene transcription and protein expression after exposure to UVB and UVA, respectively. Keratinocyte cells, treated with or without UV, were analyzed by TMT-labeled MS/MS spectra and RNA-sequencing. A common set of genes/proteins was found to be impacted by both UVA and UVB and the other differential genes/proteins showed wavelength specificity. The common set of genes/proteins were mainly involved in keratinization, lipid metabolic processes and stimulus response. The UVB specifically responsive genes/proteins were mainly related to RNA processing, gene silencing regulation and cytoskeleton organization. The UVA specifically responsive genes/proteins were mainly involved in vesiclemediated transport and oxygen-containing compound response. Meanwhile, the hub differential genes/proteins in each set were identified by protein-protein interaction networks and cluster analysis. This work provided a global view of the similar and differential molecular mechanisms of UVB-and UVA-induced cell damage in keratinocytes, which would be beneficial for further studies in the prevention or treatment of UV-related pathologies.

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“…Based on our previous research, the combination of transcriptomic and proteomic analyses in our work revealed common and differential genes or proteins in human primary keratinocytes exposed to UVA and UVB [21]. By combing protein-protein interactions (PPI) and molecular complex detection method (MCODE) analyses, hub genes or proteins were discovered in each group, which could be the basis for subsequent research on the mechanism of skin damage caused by UV radiation.…”

“…In laboratory studies, the doses of UVA and UVB radiation given to cultured cells are typically higher than the ambient levels of these types of radiation that would be encountered during normal sun exposure. We chose 10 J/cm 2 of UVA or 30 mJ/cm 2 UVB as irradiation dose based on the previous study [21], which have shown that 10 J/cm 2 of UVA or 30 mJ/cm 2 UVB can cause cell damage and decrease cell survival rates without causing excessive harm and affecting cell growth status.…”

“…Based on our previous study [21], we performed multiomics to characterize the common and different changes in gene transcription after UVB and UVA exposure. Through differentially expressed genes (DEGs) analysis of HaCaT cells induced by UVA and UVB, gene transcription significantly regulated by UVA and UVB radiation was defined as "TCG"; gene transcription specifically regulated by UVB radiation was defined as "TBG"; UVA radiation specific regulated gene transcription is defined as "TAG".…”