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
  • 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: [email protected].
  • 6. The People's Hospital of Danyang & Affiliated Danyang Hospital of Nantong University, Danyang 212300, China. Electronic address: [email protected].
  • 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: [email protected].
  • 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: [email protected].
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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