Chronic exposure to microcystin-leucine-arginine induces epithelial hyperplasia and inflammation in the mouse bladder

• Published in: Ecotoxicology and environmental safety 2022-10, Vol.244, p.114033-114033, Article 114033
• Main Authors: Zhang, Shaoru, Wu, Weidong, Peng, Yi, Liu, Lingyi, Zhang, Yaling, Wang, Rong, Chen, Zhenshi, Chu, Lei, Zhang, Xiajun, Bu, Qiang, Jiang, Dongfang, Wang, Jian, Wang, Yong, Wang, Lihui
• Format: Article
• Language: English
• Subjects: Bladder epithelial; Hyperplasia; Inflammation; Microcystin-leucine-arginine; SV-HUC-1 cells
• ISSN: 0147-6513; 1090-2414
• DOI: 10.1016/j.ecoenv.2022.114033

Microcystin-leucine-arginine (MC-LR) is a cyclic heptapeptide compound produced by cyanobacteria with strong cytotoxicity. Previous studies have confirmed that MC-LR could exert toxic effects on the genitourinary system, but there are few reports about its toxicity to the bladder. In this study, we investigated the effects of MC-LR on mouse bladder and human bladder epithelial cells (SV-HUC-1 cells). We observed that the bladder weight and the number of bladder epithelial cells were markedly increased in mice following chronic low-dose exposure to MC-LR. Further investigation showed that MC-LR activates AKT/NF-kB signaling pathway to induce the production of proinflammatory cytokines TNF-α and IL-6. In addition, the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in bladder tissue was increased and the relative migration and invasion capacities of SV-HUC-1 cells were enhanced upon exposure to MC-LR. In conclusion, these results suggest that chronic exposure to MC-LR induced epithelial hyperplasia and inflammation, upregulated the expression of matrix metalloproteinases (MMPs) and promoted the migration and invasion of bladder epithelial cells, which provides a basis for further exploring the potential mechanism by which environmental factors increasing the risk of bladder cancer. •Chronic exposure to MC-LR can lead to hyperplasia of bladder epithelial in mice.•MC-LR induces bladder inflammation by activating AKT/NF-kB signaling pathway.•MC-LR upregulates the expression of MMP-9/MMP-2 in the mouse bladder.•MC-LR promotes the migration and invasion of bladder epithelial cells.