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Int. J. Mol. Sci. 2017, 18(8), 1656; doi:10.3390/ijms18081656

Nrf2-Knockout Protects from Intestinal Injuries in C57BL/6J Mice Following Abdominal Irradiation with γ Rays

1
Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China
2
Department of Cellular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
*
Author to whom correspondence should be addressed.
Received: 7 July 2017 / Revised: 23 July 2017 / Accepted: 27 July 2017 / Published: 31 July 2017
(This article belongs to the Special Issue Nrf2 in Redox Signaling: A Double Edged Sword)
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Abstract

Radiation-induced intestinal injuries (RIII) commonly occur in patients who suffer from pelvic or abdominal cancer. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a key transcriptional regulator of antioxidant, and the radioprotective role of Nrf2 is found in bone marrow, lung, and intestine, etc. Here, we investigated the effect of Nrf2 knockout on radiation-induced intestinal injuries using Nrf2 knockout (Nrf2−/−) mice and wild-type (Nrf2+/+) C57BL/6J mice following 13 Gy abdominal irradiation (ABI). It was found that Nrf2 knockout promoted the survival of irradiated mice, protected the crypt-villus structure of the small intestine, and elevated peripheral blood lymphocyte count and thymus coefficients. The DNA damage of peripheral blood lymphocytes and the apoptosis of intestinal epithelial cells (IECs) of irradiated Nrf2−/− mice were decreased. Furthermore, compared with that of Nrf2+/+ mice, Nrf2 knockout increased the number of Lgr5+ intestinal stem cells (ISCs) and their daughter cells including Ki67+ transient amplifying cells, Villin+ enterocytes, and lysozyme+ Paneth cells. Nuclear factor-κB (NF-κB) was accumulated in the crypt base nuclei of the small intestine, and the mRNA expression of NF-κB target genes Bcl-2, uPA, and Xiap of the small intestine from irradiated Nrf2−/− mice were increased. Collectively, Nrf2 knockout has the protective effect on small intestine damage following abdominal irradiation by prompting the proliferation and differentiation of Lgr5+ intestinal stem cells and activation of NF-κB. View Full-Text
Keywords: Nrf2; intestinal injury; abdominal irradiation; intestinal stem cells; NF-κB Nrf2; intestinal injury; abdominal irradiation; intestinal stem cells; NF-κB
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Yang, W.; Sun, Z.; Yang, B.; Wang, Q. Nrf2-Knockout Protects from Intestinal Injuries in C57BL/6J Mice Following Abdominal Irradiation with γ Rays. Int. J. Mol. Sci. 2017, 18, 1656.

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