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Protective effects of activated vitamin D receptor on radiation-induced intestinal injury |
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| Authors: | Yuhan Lin Penglin Xia Fangyu Cao Cheng Zhang Yajie Yang Haitao Jiang Haishan Lin Hu Liu Ruling Liu Xiaodong Liu Jianming Cai |
| Affiliation: | 1. School of Public Health and Management, Wenzhou Medical University, Zhejiang, China;2. Department of Radiation Medicine, Faculty of Naval Medicine, Naval Military Medical University, Shanghai, China Contribution: Investigation (equal);3. Incubation Base for Undergraduates' Innovative Practice in Department of Radiation Medicine, Faculty of Naval Medicine, Naval Military Medical University, Shanghai, China;4. School of Public Health and Management, Wenzhou Medical University, Zhejiang, China Contribution: Investigation (equal);5. Incubation Base for Undergraduates' Innovative Practice in Department of Radiation Medicine, Faculty of Naval Medicine, Naval Military Medical University, Shanghai, China Contribution: Investigation (equal);6. Department of Oral and maxillofacial Trauma and Orthognathic Surgery, Stomatological Hospital of Zunyi Medical University, Zunyi, China;7. Cancer Centre, Beijing Friendship Hospital, Capital Medical University, Beijing, China Contribution: Writing - original draft (equal);8. Department of Radiation Medicine, Faculty of Naval Medicine, Naval Military Medical University, Shanghai, China Contribution: Resources (equal);9. Department of Radiation Medicine, Faculty of Naval Medicine, Naval Military Medical University, Shanghai, China |
| Abstract: | Radiation-induced intestinal injury (RIII) is a common complication after radiation therapy in patients with pelvic, abdominal, or retroperitoneal tumours. Recently, in the model of DSS (Dextran Sulfate Sodium Salt) -induced intestinal inflammatory injury, it has been found in the study that transgenic mice expressing hVDR in IEC (Intestinal Epithelial Cell) manifest highly anti-injury properties in colitis, suggesting that activated VDR in the epithelial cells of intestine may inhibit colitis by protecting the mucosal epithelial barrier. In this study, we investigated the effect of the expression and regulation of VDR on the protection of RIII, and the radiosensitivity in vitro experiments, and explored the initial mechanism of VDR in regulating radiosensitivity of IEC. As a result, we found that the expression of VDR in intestinal tissues and cells in mice can be induced by ionizing radiation. VDR agonists are able to prolong the average survival time of mice after radiation and reduce the radiation-induced intestinal injury. For lack of vitamin D, the radiosensitivity of intestinal epithelial cells in mice increased, which can be reduced by VDR activation. Ensuing VDR activation, the radiation-induced intestinal stem cells damage is decreased, and the regeneration and differentiation of intestinal stem cells is promoted as well. Finally, on the basis of sequencing analysis, we validated and found that VDR may target the HIF/PDK1 pathway to mitigate RIII. We concluded that agonism or upregulation of VDR expression attenuates radiation-induced intestinal damage in mice and promotes the repair of epithelial damage in intestinal stem cells. |
| Keywords: | HIF/PDK1 radiation protection radiation-induced intestinal injury tumour radiotherapy vitamin D |