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Altered bile acid metabolism in skin tissues in response to ionizing radiation: deoxycholic acid (DCA) as a novel treatment for radiogenic skin injury

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机构: [1]Department of Radiation Medicine, Laboratory of Radiation Medicine, West China School of Basic Medical Sciences &amp [2]Forensic Medicine, Sichuan University, Chengdu, China. [2]School of Radiation Medicine and Protection, State Key Laboratory of Radiation Medicine, Soochow University, Suzhou, China. [3]The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu, China. [4]Key Laboratory of Radiation Physics and Technology of Ministry of Education, Institute of Nuclear Science and Technology, Sichuan University, Chengdu, China. [5]NHC Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, Mianyang, China.
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关键词: Ionizing radiation skin injury bile acid metabolism deoxycholic acid (DCA)

摘要:
Radiogenic skin injury (RSI) is a common complication during cancer radiotherapy or accidental exposure to radiation. The aim of this study is to investigate the metabolism of bile acids (BAs) and their derivatives during RSI.Rat skin tissues were irradiated by an X-ray linear accelerator. The quantification of BAs and their derivatives were performed by liquid chromatography-mass spectrometry (LC-MS)-based quantitative analysis. Key enzymes in BA biosynthesis were analyzed from single-cell RNA sequencing (scRNA-Seq) data of RSI in the human patient and animal models. The in vivo radioprotective effect of deoxycholic acid (DCA) was detected in irradiated SD rats.Twelve BA metabolites showed significant differences during the progression of RSI. Among them, the levels of cholic acid (CA), DCA, muricholic acid (MCA), chenodeoxycholic acid (CDCA), glycocholic acid (GCA), glycohyodeoxycholic acid (GHCA), 12-ketolithocholic acid (12-ketoLCA) and ursodeoxycholic acid (UDCA) were significantly elevated in irradiated skin, whereas lithocholic acid (LCA), tauro-β-muricholic acid (Tβ-MCA) and taurocholic acid (TCA) were significantly decreased. Additionally, the results of scRNA-Seq indicated that genes involved in 7a-hydroxylation process, the first step in BA synthesis, showed pronounced alterations in skin fibroblasts or keratinocytes. The alternative pathway of BA synthesis is more actively altered than the classical pathway after ionizing radiation. In the model of rat radiogenic skin damage, DCA promoted wound healing and attenuated epidermal hyperplasia.Ionizing radiation modulates the metabolism of BAs. DCA is a prospective therapeutic agent for the treatment of RSI.

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出版当年[2023]版:
大类 | 4 区 医学
小类 | 3 区 生物学 3 区 核科学技术 4 区 核医学
最新[2023]版:
大类 | 4 区 医学
小类 | 3 区 生物学 3 区 核科学技术 4 区 核医学
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第一作者机构: [1]Department of Radiation Medicine, Laboratory of Radiation Medicine, West China School of Basic Medical Sciences &amp
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通讯机构: [1]Department of Radiation Medicine, Laboratory of Radiation Medicine, West China School of Basic Medical Sciences &amp [2]Forensic Medicine, Sichuan University, Chengdu, China. [2]School of Radiation Medicine and Protection, State Key Laboratory of Radiation Medicine, Soochow University, Suzhou, China. [3]The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu, China. [5]NHC Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, Mianyang, China. [*1]Department of Radiation Medicine, West China Second University Hospital,Sichuan University, Chengdu 610041, China [*2]Department of Plastic Surgery, The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu 610051, China
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