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

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...

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Bibliographic Details
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
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Summary: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.
ISSN:2072-6643
2072-6643
DOI:10.3390/nu13092910