Heat Killed Salmonella typhimurium Protects Intestine Against Radiation Injury Through Wnt Signaling Pathway

Yuanyuan Chen; Kun Cao; Hu Liu; Tingting Liu; Lei Liu; Hongran Qin; Zebin Liao; Xuguang Hu; Bailong Li; Cong Liu; Jianming Cai; Jianguo Cui; Fu Gao; Yanyong Yang

doi:10.1155/2021/5550956

Heat Killed Salmonella typhimurium Protects Intestine Against Radiation Injury Through Wnt Signaling Pathway

J Oncol. 2021 Jun 18:2021:5550956. doi: 10.1155/2021/5550956. eCollection 2021.

Authors

Yuanyuan Chen^#¹, Kun Cao^#¹, Hu Liu^#¹, Tingting Liu¹, Lei Liu¹, Hongran Qin^{1

2}, Zebin Liao^{1

3}, Xuguang Hu⁴, Bailong Li¹, Cong Liu¹, Jianming Cai¹, Jianguo Cui¹, Fu Gao¹, Yanyong Yang¹

Affiliations

¹ Department of Radiation Medicine, Faculty of Naval Medicine, Naval Medical University, Shanghai, China.
² Department of Nuclear Radiation, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China.
³ Department of Radiation Medicine, Beijing Institute of Radiation Medicine, Beijing, China.
⁴ Department of Gastrointestinal Surgery, Changhai Hospital, Shanghai, China.

^# Contributed equally.

Abstract

Gastrointestinal (GI) toxicity caused by ionizing radiation (IR) is a dose limiting factor in radiotherapy and a great threat for individual nuclear-related military missions. However, there are currently no available strategies to effectively prevent the damage on the intestine induced by IR. In the present study, the protective activity of Heat Killed Salmonella typhimurium (HKST) on intestine against IR was investigated. Through mouse intestinal organoids and whole body irradiation of mice, we found that the pretreatment with HKST significantly preserved the structure of small intestine upon IR exposure and promoted the proliferation of intestinal cells post-IR. Further study revealed that the radioprotective effects of HKST were involved in DNA damage response (DDR) signaling. Moreover, the stimulation of DDR signaling by HKST upon radiation damage was mediated by Wnt signaling, in which the inhibition of Wnt signaling diminished the radioprotective effects of HKST. To sum up, our study suggested HKST as a potential radioprotectant used for prevention of IR-induced GI toxicity.