Mercury exposure induces cytoskeleton disruption and loss of renal function through epigenetic modulation of MMP9 expression

Toxicology
Hafizurrahman KhanVikas Srivastava

Abstract

Mercury is one of the major heavy metal pollutants occurring in elemental, inorganic and organic forms. Due to ban on most inorganic mercury containing products, human exposure to mercury generally occurs as methylmercury (MeHg) by consumption of contaminated fish and other sea food. Animal and epidemiological studies indicate that MeHg affects neural and renal function. Our study is focused on nephrotoxic potential of MeHg. In this study, we have shown for the first time how MeHg could epigenetically modulate matrix metalloproteinase 9(MMP9) to promote nephrotoxicity using an animal model of sub chronic MeHg exposure. MeHg caused renal toxicity as was seen by increased levels of serum creatinine and expression of early nephrotoxicity markers (KIM-1, Clusterin, IP-10, and TIMP). MeHg exposure also correlated strongly with induction of MMP9 mRNA and protein in a dose dependent manner. Further, while induction of MMP9 promoted cytoskeleton disruption and loss of cell-cell adhesion (loss of F-actin, Vimentin and Fibronectin), inhibition of MMP9 was found to reduce these disruptions. Mechanistic studies by ChIP analysis showed that MeHg modulated MMP9 by promoting demethylation of its regulatory region to increase its expression. B...Continue Reading

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Citations

Apr 5, 2020·High-throughput·Alessio Metere, Claire E Graves
Nov 14, 2019·Toxics·Megan Culbreth, Michael Aschner
Jan 19, 2021·ACS Biomaterials Science & Engineering·Peiran ZhuYubing Sun
Oct 1, 2021·Environmental Science and Pollution Research International·Lorena Díaz de León-MartínezRogelio Flores-Ramírez
Jun 17, 2020·Ecotoxicology and Environmental Safety·Sanjay SainiNaveen Kumar Gautam
Nov 24, 2021·Advanced Healthcare Materials·Angela M GutierrezJ Zach Hilt

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