| Literature DB >> 26351675 |
Masahiro Hachisuga1, Shinya Oki2, Keiko Kitajima2, Satomi Ikuta2, Tomoyuki Sumi2, Kiyoko Kato3, Norio Wake3, Chikara Meno4.
Abstract
Congenital heart defects with heterotaxia are associated with pregestational diabetes mellitus. To provide insight into the mechanisms underlying such diabetes-related heart defects, we examined the effects of high-glucose concentrations on formation of the left-right axis in mouse embryos. Expression of Pitx2, which plays a key role in left-right asymmetric morphogenesis and cardiac development, was lost in the left lateral plate mesoderm of embryos of diabetic dams. Embryos exposed to high-glucose concentrations in culture also failed to express Nodal and Pitx2 in the left lateral plate mesoderm. The distribution of phosphorylated Smad2 revealed that Nodal activity in the node was attenuated, accounting for the failure of left-right axis formation. Consistent with this notion, Notch signal-dependent expression of Nodal-related genes in the node was also down-regulated in association with a reduced level of Notch signaling, suggesting that high-glucose concentrations impede Notch signaling and thereby hinder establishment of the left-right axis required for heart morphogenesis.Entities:
Keywords: congenital heart defects; diabetes; heterotaxia; left–right axis
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Year: 2015 PMID： 26351675 PMCID： PMC4586861 DOI： 10.1073/pnas.1504529112
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205