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Published on: March 10, 2017
Stimulation effect of microcystin-LR on matrix metalloproteinase-2/-9 expression in mouse liver
Xu-Xiang Zhang1, Zongyao Zhang, Ziyi Fu
1State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210046, China.
Abstract:
In order to investigate the potential effects of microcystin-LR (MC-LR) on the expression of metalloproteinases (MMPs), Mice were orally administered with MC-LR in drinking water (0, 1, 40 and 80 μg/L) for 180 d, and hepatic MMP-2/-9 expression was evaluated at the levels of enzyme activity, protein level and mRNA expression. Histopathologic observation showed the obvious hepatic lymphocyte infiltration and fatty degeneration in the mice exposed to 40 and 80 μg/L MC-LR. Immunohistochemical staining and enzyme-linked immunosorbent assay (ELISA) revealed that excess MMP-2/-9 proteins were produced in livers of the mice exposed to MC-LR at the higher concentrations. Hepatic MMP-9 level was elevated from 0.6 ng/g liver weight in control to 1.4 ng/g liver weight in 80-μg/L group, but a slight increase was found for MMP-2 level. Real time PCR showed that MMP-2/-9 mRNA expression was up-regulated by 6.9 fold and 5.0 fold after 80-μg/L-MC treatment, respectively. MMP-2/-9 expression showed a good dose-dependent manner at both protein and mRNA levels. ELISA demonstrated that MC-LR stimulated phosphorylation of mitogen-activated protein kinases, a potential signal transduction pathway of the MMP-2/-9 expression alteration. This study revealed a significant alteration in hepatic MMP-2/-9 expression induced by MC-LR, which might be involved in cell invasion and metastasis.
Insights
Microcystin-LR (MC-LR) exposure in mice significantly increased hepatic matrix metalloproteinase (MMP)-2 and MMP-9 expression at protein and mRNA levels. This suggests MC-LR may contribute to liver damage and potentially cell metastasis.
Area of Science:
- Environmental Toxicology
- Hepatology
- Molecular Biology
Background:
- Microcystin-LR (MC-LR) is a potent hepatotoxin produced by cyanobacteria.
- Matrix metalloproteinases (MMPs) play crucial roles in tissue remodeling, inflammation, and cancer progression.
Purpose of the Study:
- To investigate the impact of chronic MC-LR exposure on hepatic MMP-2 and MMP-9 expression in mice.
- To elucidate the potential signaling pathways involved in MC-LR-induced MMP alterations.
Main Methods:
- Mice were orally administered varying doses of MC-LR (0, 1, 40, 80 μg/L) for 180 days.
- Hepatic MMP-2/-9 levels were assessed via enzyme activity, protein quantification (ELISA), and mRNA expression (Real-time PCR).
- Histopathology and immunohistochemistry were used to evaluate liver damage and protein localization. MAPK phosphorylation was also analyzed.
Main Results:
- MC-LR exposure led to dose-dependent hepatic lymphocyte infiltration and fatty degeneration.
- Significant increases in MMP-2 and MMP-9 protein and mRNA levels were observed, particularly at higher MC-LR concentrations.
- MMP-9 levels increased from 0.6 ng/g to 1.4 ng/g liver weight in the highest dose group.
- MMP-2/-9 mRNA expression was upregulated by 6.9-fold and 5.0-fold, respectively, at 80 μg/L MC-LR.
- MC-LR stimulated mitogen-activated protein kinase (MAPK) phosphorylation, suggesting a role in MMP regulation.
Conclusions:
- Chronic MC-LR exposure induces significant alterations in hepatic MMP-2/-9 expression in a dose-dependent manner.
- These MMP changes may contribute to MC-LR-induced liver pathology, including inflammation and fatty degeneration.
- The observed alterations in MMP expression might be implicated in cell invasion and metastasis, warranting further investigation.
