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Received February 2, 2022
Accepted February 24, 2022
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Multiomics characterization of dose- and time-dependent effects of ionizing radiation on human skin keratinocytes
Won-Suk Song
Jae-Seung Lee
Jun Woo Lim
JiEung Kim1
Sung-Hyun Jo
Ji-Eun Kwon
Ji-Hyeon Park
Sang Hyoun Choi2
Dongchan Jang1
Il Won Kim
Jae Hyun Jeong
Yun-Gon Kim†
Department of Chemical Engineering, Soongsil University, Seoul 06978, Korea 1Department of Nuclear and Quantum Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea 2Research Team of Radiological Physics and Engineering, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Korea
Korean Journal of Chemical Engineering, September 2022, 39(9), 2455-2464(10), 10.1007/s11814-022-1095-2
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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 2Gy 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 2Gy 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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Ackermann K, Borgia SL, Korting HC, Mewes KR, Schäfer-Korting M, Skin Pharmacol. Physiol., 23, 105 (2010)
D'Orazio J, Jarrett S, Amaro-Ortiz A, Scott T, Int. J. Mol. Sci., 14, 12222 (2013)
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