Long-term environmental levels of microcystin-LR exposure induces colorectal chronic inflammation, fibrosis and barrier disruption via CSF1R/Rap1b signaling pathway.

Journal of hazardous materials 2022 Oct 15

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Microcystin-LR (MC-LR) is a very common toxic cyanotoxins threating ecosystems and the public health. This study aims to explore the long-term effects and potential toxicity mechanisms of MC-LR exposure at environmental levels on colorectal injury. We performed histopathological, biochemical indicator and multi-omics analyses in mice with low-dose MC-LR exposure for 12 months. Long-term environmental levels of MC-LR exposure caused epithelial barrier disruption, inflammatory cell infiltration and an increase of collagen fibers in mouse colorectum. Integrated proteotranscriptomics revealed differential expression of genes/proteins, including CSF1R, which were mainly involved in oxidative stress-induced premature senescence and inflammatory response. MC-LR induced chronic inflammation and fibrosis through oxidative stress and CSF1R/Rap1b signaling pathway were confirmed in cell models. We found for the first time that long-term environmental levels of MC-LR exposure caused colorectal chronic inflammation, fibrosis and barrier disruption via a novel CSF1R/Rap1b signaling pathway. Moreover, MC-LR changed the gut microbiota and microbial-related metabolites in a vicious cycle aggravating colorectal injury. These findings provide novel insights into the effects and toxic mechanisms of MC-LR and suggest strategies for the prevention and treatment of MC-caused intestinal diseases. Copyright © 2022 Elsevier B.V. All rights reserved.

Citation

Yue Yang, Hui Wang, Xiaoyan Wang, Ling Chen, Wenya Liu, Danping Cai, Shuxiang Deng, Hanyu Chu, Ying Liu, Xiangling Feng, Jihua Chen, Mengshi Chen, Chengkun Wang, Ran Liu, Yuepu Pu, Zhen Ding, Deliang Cao, Dingxin Long, Yi Cao, Fei Yang. Long-term environmental levels of microcystin-LR exposure induces colorectal chronic inflammation, fibrosis and barrier disruption via CSF1R/Rap1b signaling pathway. Journal of hazardous materials. 2022 Oct 15;440:129793