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Published on: February 23, 2019
Arsenic enhances matrix metalloproteinase-14 expression in fibroblasts
Masashi Kato1, Khaled Hossain, Machiko Iida
1Unit of Environmental Health Sciences, Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Aichi, Japan. katomasa@isc.chubu.ac.jp
Abstract:
This study focused on the effects of arsenic (As) on fibroblast-derived matrix metalloproteinase (MMP)-2 and -14 levels, as these proteins were reported to be associated with tumor progression. Arsenic was found to promote production of the fibroblast-derived active form of MMP-2. Further, As at 100 or 1000 microM increased MMP-14 expression levels in fibroblasts. In addition, 1000 microM mercury (Hg) but not As increased pro-MMP-2 protein, which is involved in the conversion of the proenzyme into its active form. Since MMP-14 is an activator of pro-MMP-2, data suggest that As promotes production of fibroblast-derived active form of MMP-2 through increased expression of MMP-14. Evidence indicates that As appeared to be less effective than Hg in the conversion of pro-MMP-2 into its active form.
Insights
Arsenic exposure increases fibroblast production of active matrix metalloproteinase (MMP)-2 by upregulating MMP-14. This suggests arsenic may promote tumor progression by activating MMP-2, though less effectively than mercury.
Area of Science:
- Biochemistry
- Toxicology
- Cancer Biology
Background:
- Matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-14, are implicated in tumor progression.
- Fibroblast-derived MMPs play a crucial role in extracellular matrix remodeling.
- Understanding the impact of environmental toxins like arsenic on these proteins is vital.
Purpose of the Study:
- To investigate the effects of arsenic (As) on fibroblast-derived MMP-2 and MMP-14 levels.
- To elucidate the mechanism by which arsenic influences the active form of MMP-2.
- To compare the effects of arsenic and mercury (Hg) on MMP-2 activation.
Main Methods:
- Fibroblast cell cultures were treated with varying concentrations of arsenic (As) and mercury (Hg).
- Expression levels of MMP-2 and MMP-14 were analyzed.
- Levels of pro-MMP-2 and active MMP-2 were quantified.
Main Results:
- Arsenic exposure significantly increased the production of the active form of fibroblast-derived MMP-2.
- Arsenic treatment elevated MMP-14 expression levels in fibroblasts.
- Mercury (1000 microM) increased pro-MMP-2 protein, while arsenic did not.
- MMP-14 acts as an activator of pro-MMP-2.
Conclusions:
- Arsenic promotes the production of active fibroblast-derived MMP-2 primarily through the upregulation of MMP-14 expression.
- These findings suggest a potential mechanism for arsenic-induced tumor progression.
- Arsenic is less potent than mercury in converting pro-MMP-2 to its active form.