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

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

  • Ecotoxicol Environ Saf. 2022 Oct 1;244:114033. doi: 10.1016/j.ecoenv.2022.114033.
Shaoru Zhang 1 Weidong Wu 2 Yi Peng 2 Lingyi Liu 3 Yaling Zhang 4 Rong Wang 4 Zhenshi Chen 2 Lei Chu 2 Xiajun Zhang 2 Qiang Bu 2 Dongfang Jiang 5 Jian Wang 6 Yong Wang 7 Lihui Wang 8
Affiliations

Affiliations

  • 1 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.
  • 2 The People's Hospital of Danyang & Affiliated Danyang Hospital of Nantong University, Danyang 212300, China.
  • 3 School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
  • 4 State Key Laboratory of Analytical Chemistry for Life Science & Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing 210093, China.
  • 5 The People's Hospital of Danyang & Affiliated Danyang Hospital of Nantong University, Danyang 212300, China. Electronic address: 13912823872@163.com.
  • 6 The People's Hospital of Danyang & Affiliated Danyang Hospital of Nantong University, Danyang 212300, China. Electronic address: wangjian4068@aliyun.com.
  • 7 State Key Laboratory of Analytical Chemistry for Life Science & Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing 210093, China. Electronic address: yongwang@nju.edu.cn.
  • 8 State Key Laboratory of Analytical Chemistry for Life Science & Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing 210093, China. Electronic address: lihuiwang@nju.edu.cn.
Abstract

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.

Keywords

Bladder epithelial; Hyperplasia; Inflammation; Microcystin-leucine-arginine; SV-HUC-1 cells.

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