Akt promotes Endocardial-Mesenchyme Transition

Persistent Link:
http://hdl.handle.net/10150/610167
Title:
Akt promotes Endocardial-Mesenchyme Transition
Author:
Meadows, Kafi; Iyer, Seema; Stevens, Mark; Wang, Duanning; Shechter, Sharon; Perruzzi, Carole; Camenisch, Todd; Benjamin, Laura
Affiliation:
Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Department of Pharmacology and Toxicology, College of Pharmacy, The University of Arizona, Tucson, Arizona, USA
Issue Date:
2009
Publisher:
BioMed Central
Citation:
Journal of Angiogenesis Research 2009, 1:2 doi:10.1186/2040-2384-1-2
Journal:
Journal of Angiogenesis Research
Rights:
© 2009 Meadows et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0)
Collection Information:
This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.
Abstract:
Endothelial to mesenchyme transition (EndMT) can be observed during the formation of endocardial cushions from the endocardium, the endothelial lining of the atrioventricular canal (AVC), of the developing heart at embryonic day 9.5 (E9.5). Many regulators of the process have been identified; however, the mechanisms driving the initial commitment decision of endothelial cells to EndMT have been difficult to separate from processes required for mesenchymal proliferation and migration. We have several lines of evidence that suggest a central role for Akt signaling in committing endothelial cells to enter EndMT. Akt1 mRNA was restricted to the endocardium of endocardial cushions while they were forming. The PI3K/Akt signaling pathway is necessary for mesenchyme outgrowth, as sprouting was inhibited in AVC explant cultures treated with the PI3K inhibitor LY294002. Furthermore, endothelial marker, VE-cadherin, was downregulated and mesenchyme markers, N-cadherin and Snail, were induced in response to expression of a constitutively active form of Akt1 (myrAkt1) in endothelial cells. Finally, we isolated the function of Akt1 signaling in the commitment to the transition using a transgenic model where myrAkt1 was pulsed only in endocardial cells and turned off after EndMT initiation. In this way, we determined that increased Akt signaling in the endocardium drives EndMT and discounted its other functions in cushion mesenchymal cells.
EISSN:
2040-2384
DOI:
10.1186/2040-2384-1-2
Version:
Final published version
Additional Links:
http://www.jangiogenesis.com/content/1/1/2

Full metadata record

DC FieldValue Language
dc.contributor.authorMeadows, Kafien
dc.contributor.authorIyer, Seemaen
dc.contributor.authorStevens, Marken
dc.contributor.authorWang, Duanningen
dc.contributor.authorShechter, Sharonen
dc.contributor.authorPerruzzi, Caroleen
dc.contributor.authorCamenisch, Todden
dc.contributor.authorBenjamin, Lauraen
dc.date.accessioned2016-05-20T09:00:10Z-
dc.date.available2016-05-20T09:00:10Z-
dc.date.issued2009en
dc.identifier.citationJournal of Angiogenesis Research 2009, 1:2 doi:10.1186/2040-2384-1-2en
dc.identifier.doi10.1186/2040-2384-1-2en
dc.identifier.urihttp://hdl.handle.net/10150/610167-
dc.description.abstractEndothelial to mesenchyme transition (EndMT) can be observed during the formation of endocardial cushions from the endocardium, the endothelial lining of the atrioventricular canal (AVC), of the developing heart at embryonic day 9.5 (E9.5). Many regulators of the process have been identifieden
dc.description.abstracthowever, the mechanisms driving the initial commitment decision of endothelial cells to EndMT have been difficult to separate from processes required for mesenchymal proliferation and migration. We have several lines of evidence that suggest a central role for Akt signaling in committing endothelial cells to enter EndMT. Akt1 mRNA was restricted to the endocardium of endocardial cushions while they were forming. The PI3K/Akt signaling pathway is necessary for mesenchyme outgrowth, as sprouting was inhibited in AVC explant cultures treated with the PI3K inhibitor LY294002. Furthermore, endothelial marker, VE-cadherin, was downregulated and mesenchyme markers, N-cadherin and Snail, were induced in response to expression of a constitutively active form of Akt1 (myrAkt1) in endothelial cells. Finally, we isolated the function of Akt1 signaling in the commitment to the transition using a transgenic model where myrAkt1 was pulsed only in endocardial cells and turned off after EndMT initiation. In this way, we determined that increased Akt signaling in the endocardium drives EndMT and discounted its other functions in cushion mesenchymal cells.en
dc.language.isoenen
dc.publisherBioMed Centralen
dc.relation.urlhttp://www.jangiogenesis.com/content/1/1/2en
dc.rights© 2009 Meadows et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0)en
dc.titleAkt promotes Endocardial-Mesenchyme Transitionen
dc.typeArticleen
dc.identifier.eissn2040-2384en
dc.contributor.departmentDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USAen
dc.contributor.departmentDepartment of Pharmacology and Toxicology, College of Pharmacy, The University of Arizona, Tucson, Arizona, USAen
dc.identifier.journalJournal of Angiogenesis Researchen
dc.description.collectioninformationThis item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen
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