Vitamin D Receptor Protects against Radiation-Induced Intestinal Injury in Mice via Inhibition of Intestinal Crypt Stem/Progenitor Cell Apoptosis

• Published in: Nutrients 2021-08, Vol.13 (9), p.2910
• Main Authors: Li, Wusun, Lin, Yingying, Luo, Yujia, Wang, Yuqi, Lu, Yao, Li, Yixuan, Guo, Huiyuan
• Format: Article
• Language: English
• Subjects: Antibodies; Apoptosis; Calciferol; Cancer therapies; Cell proliferation; Cells (biology); crypt stem/progenitor cell; Crypts; Deoxyribonucleic acid; DNA; DNA damage; Gene expression; Inflammatory bowel disease; Intestine; Ionizing radiation; Laboratory animals; Lactose; Medical research; Pmaip1; Progenitor cells; Proteins; Radiation damage; Radiation effects; Radiation injuries; Radiation therapy; siRNA; Stem cells; Transfection; Vitamin D; Vitamin D receptors; vitamin D/vitamin D receptor
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu13092910

It is urgent to seek new potential targets for the prevention or relief of gastrointestinal syndrome in clinical radiation therapy for cancers. Vitamin D, mediated through the vitamin D receptor (VDR), has been identified as a protective nutrient against ionizing radiation (IR)-induced damage. This study investigated whether VDR could inhibit IR-induced intestinal injury and explored underlying mechanism. We first found that vitamin D induced VDR expression and inhibited IR-induced DNA damage and apoptosis in vitro. VDR was highly expressed in intestinal crypts and was critical for crypt stem/progenitor cell proliferation under physiological conditions. Next, VDR-deficient mice exposed to IR significantly increased DNA damage and crypt stem/progenitor cell apoptosis, leading to impaired intestinal regeneration as well as shorter survival time. Furthermore, VDR deficiency activated the Pmaip1-mediated apoptotic pathway of intestinal crypt stem/progenitor cells in IR-treated mice, whereas inhibition of Pmaip1 expression by siRNA transfection protected against IR-induced cell apoptosis. Therefore, VDR protects against IR-induced intestinal injury through inhibition of crypt stem/progenitor cell apoptosis via the Pmaip1-mediated pathway. Our results reveal the importance of VDR level in clinical radiation therapy, and targeting VDR may be a useful strategy for treatment of gastrointestinal syndrome.