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Multiomics characterization of dose- and time-dependent effects of ionizing radiation on human skin keratinocytes

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Abstract

Ionizing radiation is used for various purposes, such as cancer treatment and medical diagnosis. As skin keratinocytes are frequently exposed to various radiation doses, the risk of developing skin diseases is also increasing. However, knowledge of the biological response of human keratinocytes to radiation doses and time-points is still limited despite its importance. Here, we characterized the proteomic and metabolomic changes in HEKn cells on day 0 and 2 after irradiation with control, 0.1, 0.5, and 2 Gy to identify biological effects depending on IR dose and time. First, we found that the expression levels of proteins and metabolites involved in energy metabolism, DNA repair system, and epidermal cornification were changed following irradiation. In particular, fumarate and fumarate hydratase, which promote DNA repair, were significantly increased in response to irradiation with 2 Gy on day 2. Furthermore, all doses of IR-induced proteomic changes correlated with epidermal cornification and inhibition of cell death on day 2 after irradiation. Using a human skin 3D full-thickness model, we observed dose-dependent increases in the cornified layer and the expression of involucrin. The multiomics signatures of cellular responses depending on IR dose and time may constitute a high-value resource, providing biological effects on IR applications.

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Acknowledgements

This work was supported by the National Research Foundation of Korea (NRF-2017M3A9E4077235, NRF-2018R1D1A1B07048185, NRF-2019M2C8A2058418, NRF-2020R1A6A1A03044977) and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HP20C0210).

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  1. These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Chemical Engineering, Soongsil University, Seoul, 06978, Korea

    Won-Suk Song, Jae-Seung Lee, Jun Woo Lim, Sung-Hyun Jo, Ji-Eun Kwon, Ji-Hyeon Park, Il Won Kim, Jae Hyun Jeong & Yun-Gon Kim

  2. Department of Nuclear and Quantum Engineering, Korea Advanced Institute of Science and Technology, Daejeon, 34141, Korea

    JiEung Kim & Dongchan Jang

  3. Research Team of Radiological Physics and Engineering, Korea Institute of Radiological and Medical Sciences, Seoul, 01812, Korea

    Sang Hyoun Choi

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  1. Won-Suk Song
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Correspondence to Yun-Gon Kim.

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Song, WS., Lee, JS., Lim, J.W. et al. Multiomics characterization of dose- and time-dependent effects of ionizing radiation on human skin keratinocytes. Korean J. Chem. Eng. 39, 2455–2464 (2022). https://doi.org/10.1007/s11814-022-1095-2

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