期刊
JOURNAL OF HAZARDOUS MATERIALS
卷 391, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.jhazmat.2020.122262
关键词
Cadmium; Intestinal barrier; Enteropathogens; Goblet cells; Notch signaling pathway
资金
- National Key R&D Program of China [2018YFE0127300]
- National Natural Science Foundation of China [31972631, 31502024, 31930109]
- Innovation and Entrepreneurship Training Program for College Students of NJAU [S20190020]
- Fundamental Research Funds for the Central Universities [JCQY201906, Y0201700175]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
Whether cadmium ingestion affects the susceptibility to infection and the detailed mechanism have not been investigated. We aimed to evaluate the effects of cadmium on the intestinal mucosal barrier and Salmonella infection. We found that oral administration of cadmium caused damage to the intestinal mucosal barrier, with body weight loss, an increase in inflammation, significantly reduced Muc2 expression and goblet cell loss in the intestine. The effect of cadmium on secretory cell differentiation was further demonstrated to be regulated by the overactivation of the Notch signaling pathway by increased production of ROS both in mice and in intestinal organoids. The damage of cadmium to the intestinal barrier, and goblet cell and Paneth cells loss, dramatically increased susceptibility to enteropathogensinfection at a low dose (10(2) CFU), with a high death ratio, body weight loss and severe intestinal inflammation. However, enteropathogens susceptibility and intestinal barrier damage enhanced by cadmium was alleviated by inhibiting ROS production and Notch pathway activation, with reversion of goblet cell loss. This study indicated cadmium didn't only affect the integrity of intestinal barrier and epithelial differentiation, but also increased the risk of enteropathogenic infection from food contamination or environmental pollution, which signals an alarm for public health.
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