The People's Hospital of Danyang & Affiliated Danyang Hospital of Nantong University, Danyang 212300, China; State Key Laboratory of Analytical Chemistry for Life Science & Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing 210093, China.
The People's Hospital of Danyang & Affiliated Danyang Hospital of Nantong University, Danyang 212300, China.
Ecotoxicol Environ Saf. 2022 Oct 1;244:114033. doi: 10.1016/j.ecoenv.2022.114033. Epub 2022 Sep 5.
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.
微囊藻氨酸-亮氨酸-精氨酸（MC-LR）是一种由蓝藻产生的具有强烈细胞毒性的环状七肽化合物。先前的研究已经证实，MC-LR 可以对泌尿系统产生毒性作用，但关于其对膀胱的毒性作用的报道较少。在这项研究中，我们研究了 MC-LR 对小鼠膀胱和人膀胱上皮细胞（SV-HUC-1 细胞）的影响。我们观察到，在慢性低剂量暴露于 MC-LR 后，小鼠的膀胱重量和膀胱上皮细胞数量明显增加。进一步的研究表明，MC-LR 通过激活 AKT/NF-κB 信号通路诱导促炎细胞因子 TNF-α 和 IL-6 的产生。此外，在暴露于 MC-LR 后，膀胱组织中基质金属蛋白酶-2（MMP-2）和基质金属蛋白酶-9（MMP-9）的表达增加，SV-HUC-1 细胞的相对迁移和侵袭能力增强。总之，这些结果表明，慢性暴露于 MC-LR 诱导上皮细胞增生和炎症，上调基质金属蛋白酶（MMPs）的表达，并促进膀胱上皮细胞的迁移和侵袭，为进一步探讨环境因素增加膀胱癌风险的潜在机制提供了依据。
