Highlights
- ●Cutaneous fatty acid metabolism was altered in the early response of ionizing radiation.
- ●Fatty acid metabolism-associated ACADVL is involved in radiation-induced cell death.
Abstract
Background
Radiation-induced skin injury is a serious concern during radiotherapy and accidental
exposure to radiation.
Objective
This study aims to investigate the molecular events in early response to ionizing
radiation of skin tissues and underlying mechanism.
Methods
Mice and rats were irradiated with an electron beam. Skin tissues were used for liquid
chromatography-mass spectrometry (LC-MS)-based metabolomics, mRNA-Seq and single-cell
RNA sequencing (scRNA-Seq). Human keratinocytes (HaCaT) and skin fibroblasts (WS1)
were used for functional studies.
Results
The integrated analysis of metabolomics and transcriptomics showed that 6 key fatty
acid-associated metabolites, 9 key fatty acid-associated genes and multiple fatty
acid-associated pathways were most obviously enriched and increased in the irradiated
skins. Among them, acyl-CoA dehydrogenase very long chain (ACADVL) was investigated
in greater detail due to its most obvious expression difference and significance in
fatty acid metabolism. ScRNA-Seq of rat skin from irradiated individuals revealed
that ACADVL was expressed in all subpopulations of skin tissues, with variations at different
timepoints after radiation. Immunohistochemistry confirmed an increased ACADVL expression in the epidermis from human sample and various animal models, including
monkeys, rats and mice. The knockdown of ACADVL increased the radiosensitivity of human keratinocytes and human skin fibroblasts.
Silencing of ACADVL facilitated the expression of apoptosis and pyroptosis-related proteins following
ionizing radiation.
Conclusion
This study illustrated that cutaneous fatty acid metabolism was altered in the early
response of ionizing radiation, and fatty acid metabolism-associated ACADVL is involved
in radiation-induced cell death.
Keywords
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Article info
Publication history
Published online: January 07, 2023
Accepted:
January 4,
2023
Received in revised form:
December 11,
2022
Received:
October 11,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2023 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.
