Disruption of canonical TGFβ-signaling in murine coronary progenitor cells by low level arsenic.

Allison P, Huang T, Broka D, Parker P, Barnett JV, Camenisch TD
Toxicol Appl Pharmacol. 2013 272 (1): 147-53

PMID: 23732083 · PMCID: PMC3972124 · DOI:10.1016/j.taap.2013.04.035

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 TGFβ 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 1.34μM arsenite disrupted developmental EMT programming in murine epicardial cells causing a deficit in cardiac mesenchyme. The expression of EMT genes including TGFβ2, TGFβ receptor-3, Snail, and Has-2 are decreased in a dose-dependent manner following exposure to arsenite. TGFβ2 cell signaling is abrogated as detected by decreases in phosphorylated Smad2/3 when cells are exposed to 1.34μM 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 TGFβ2 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 TGFβ2 signals and Smad activation, and that smooth muscle cell differentiation is refractory to this arsenic toxicity.

Published by Elsevier Inc.

MeSH Terms (19)

Animals Arsenites Blotting, Western Cell Differentiation Cell Line Cell Survival Coronary Vessels Epithelial-Mesenchymal Transition Fluorescent Antibody Technique Indicators and Reagents Mesenchymal Stem Cells Mice Microfilament Proteins Muscle Proteins Myocytes, Smooth Muscle Signal Transduction Smad Proteins Stem Cells Transforming Growth Factor beta

Connections (1)

This publication is referenced by other Labnodes entities: