Nutrients (Aug 2021)

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

  • Wusun Li,
  • Yingying Lin,
  • Yujia Luo,
  • Yuqi Wang,
  • Yao Lu,
  • Yixuan Li,
  • Huiyuan Guo

DOI
https://doi.org/10.3390/nu13092910
Journal volume & issue
Vol. 13, no. 9
p. 2910

Abstract

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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.

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