DNA methylation of extracellular matrix remodeling genes in children exposed to arsenic

Tania Gonzalez-Cortes, Rogelio Recio-Vega, Robert Clark Lantz, Binh T. Chau

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Several novel mechanistic findings regarding to arsenic's pathogenesis has been reported and some of them suggest that the etiology of some arsenic induced diseases are due in part to heritable changes to the genome via epigenetic processes such as DNA methylation, histone maintenance, and mRNA expression. Recently, we reported that arsenic exposure during in utero and early life was associated with impairment in the lung function and abnormal receptor for advanced glycation endproducts (RAGE), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) sputum levels. Based on our results and the reported arsenic impacts on DNA methylation, we designed this study in our cohort of children exposed in utero and early childhood to arsenic with the aim to associate DNA methylation of MMP9, TIMP1 and RAGE genes with its protein sputum levels and with urinary and toenail arsenic levels. The results disclosed hypermethylation in MMP9 promotor region in the most exposed children; and an increase in the RAGE sputum levels among children with the mid methylation level; there were also positive associations between MMP9 DNA methylation with arsenic toenail concentrations; RAGE DNA methylation with iAs, and %DMA; and finally between TIMP1 DNA methylation with the first arsenic methylation. A negative correlation between MMP9 sputum levels with its DNA methylation was registered. In conclusion, arsenic levels were positive associated with the DNA methylation of extracellular matrix remodeling genes;, which in turn could modifies the biological process in which they are involved causing or predisposing to lung diseases.

Original languageEnglish (US)
Pages (from-to)140-147
Number of pages8
JournalToxicology and Applied Pharmacology
Volume329
DOIs
Publication statusPublished - Aug 15 2017

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Keywords

  • Arsenic
  • Children
  • DNA methylation
  • MMP9
  • RAGE
  • TIMP1

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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