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  3. 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.
PMID: 36075121 DOI: 10.1016/j.ecoenv.2022.114033
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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