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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Disruption of canonical TGF*-signaling in murine coronary progenitor cells by low level arsenic.

Authors: Allison, Patrick; Huang, Tianfang; Broka, Derrick; Parker, Patti; Barnett, Joey V; Camenisch, Todd D

Published In Toxicol Appl Pharmacol, (2013 Oct 1)

Abstract: Exposure to arsenic results in several types of cancers as well as heart disease. A major contributor to ischemic heart pathologies is coronary artery disease, however the influences by environmental arsenic in this disease process are not known. Similarly, the impact of toxicants on blood vessel formation and function during development has not been studied. During embryogenesis, the epicardium undergoes proliferation, migration, and differentiation into several cardiac cell types including smooth muscle cells which contribute to the coronary vessels. The TGF* family of ligands and receptors is essential for developmental cardiac epithelial to mesenchymal transition (EMT) and differentiation into coronary smooth muscle cells. In this in vitro study, 18hour exposure to 1.34*M arsenite disrupted developmental EMT programming in murine epicardial cells causing a deficit in cardiac mesenchyme. The expression of EMT genes including TGF*2, TGF* receptor-3, Snail, and Has-2 are decreased in a dose-dependent manner following exposure to arsenite. TGF*2 cell signaling is abrogated as detected by decreases in phosphorylated Smad2/3 when cells are exposed to 1.34*M arsenite. There is also loss of nuclear accumulation pSmad due to arsenite exposure. These observations coincide with a decrease in vimentin positive mesenchymal cells invading three-dimensional collagen gels. However, arsenite does not block TGF*2 mediated smooth muscle cell differentiation by epicardial cells. Overall these results show that arsenic exposure blocks developmental EMT gene programming in murine coronary progenitor cells by disrupting TGF*2 signals and Smad activation, and that smooth muscle cell differentiation is refractory to this arsenic toxicity.

PubMed ID: 23732083 Exiting the NIEHS site

MeSH Terms: Animals; Arsenites/toxicity*; Blotting, Western; Cell Differentiation/drug effects; Cell Line; Cell Survival/drug effects; Coronary Vessels/cytology*; Coronary Vessels/drug effects; Epithelial-Mesenchymal Transition/drug effects*; Fluorescent Antibody Technique; Indicators and Reagents; Mesenchymal Stromal Cells/drug effects; Mice; Microfilament Proteins/genetics; Muscle Proteins/genetics; Myocytes, Smooth Muscle/drug effects; Signal Transduction/drug effects*; Smad Proteins/metabolism; Stem Cells/drug effects*; Transforming Growth Factor beta/physiology*

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