Ablation of SGK1 impairs endothelial cell migration and tube formation leading to decreased neo-angiogenesis following myocardial infarction.

Serum and glucocorticoid inducible kinase 1 (SGK1) plays a pivotal role in early angiogenesis during embryonic development. In this study, we sought to define the SGK1 downstream signalling pathways in the adult heart and to elucidate their role in cardiac neo-angiogenesis and wound healing after my...

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Main Authors: Elham Zarrinpashneh, Tommaso Poggioli, Padmini Sarathchandra, Jonas Lexow, Laurent Monassier, Cesare Terracciano, Florian Lang, Federico Damilano, Jessica Q Zhou, Anthony Rosenzweig, Nadia Rosenthal, Maria Paola Santini
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3827188?pdf=render
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author Elham Zarrinpashneh
Tommaso Poggioli
Padmini Sarathchandra
Jonas Lexow
Laurent Monassier
Cesare Terracciano
Florian Lang
Federico Damilano
Jessica Q Zhou
Anthony Rosenzweig
Nadia Rosenthal
Maria Paola Santini
author_facet Elham Zarrinpashneh
Tommaso Poggioli
Padmini Sarathchandra
Jonas Lexow
Laurent Monassier
Cesare Terracciano
Florian Lang
Federico Damilano
Jessica Q Zhou
Anthony Rosenzweig
Nadia Rosenthal
Maria Paola Santini
author_sort Elham Zarrinpashneh
collection DOAJ
description Serum and glucocorticoid inducible kinase 1 (SGK1) plays a pivotal role in early angiogenesis during embryonic development. In this study, we sought to define the SGK1 downstream signalling pathways in the adult heart and to elucidate their role in cardiac neo-angiogenesis and wound healing after myocardial ischemia. To this end, we employed a viable SGK1 knockout mouse model generated in a 129/SvJ background. Ablation of SGK1 in these mice caused a significant decrease in phosphorylation of SGK1 target protein NDRG1, which correlated with alterations in NF-κB signalling and expression of its downstream target protein, VEGF-A. Disruption of these signalling pathways was accompanied by smaller heart and body size. Moreover, the lack of SGK1 led to defective endothelial cell (ECs) migration and tube formation in vitro, and increased scarring with decreased angiogenesis in vivo after myocardial infarct. This study underscores the importance of SGK1 signalling in cardiac neo-angiogenesis and wound healing after an ischemic insult in vivo.
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spelling doaj.art-956b000831b64fd4b0ff71dbce75f1f22022-12-22T02:45:48ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01811e8026810.1371/journal.pone.0080268Ablation of SGK1 impairs endothelial cell migration and tube formation leading to decreased neo-angiogenesis following myocardial infarction.Elham ZarrinpashnehTommaso PoggioliPadmini SarathchandraJonas LexowLaurent MonassierCesare TerraccianoFlorian LangFederico DamilanoJessica Q ZhouAnthony RosenzweigNadia RosenthalMaria Paola SantiniSerum and glucocorticoid inducible kinase 1 (SGK1) plays a pivotal role in early angiogenesis during embryonic development. In this study, we sought to define the SGK1 downstream signalling pathways in the adult heart and to elucidate their role in cardiac neo-angiogenesis and wound healing after myocardial ischemia. To this end, we employed a viable SGK1 knockout mouse model generated in a 129/SvJ background. Ablation of SGK1 in these mice caused a significant decrease in phosphorylation of SGK1 target protein NDRG1, which correlated with alterations in NF-κB signalling and expression of its downstream target protein, VEGF-A. Disruption of these signalling pathways was accompanied by smaller heart and body size. Moreover, the lack of SGK1 led to defective endothelial cell (ECs) migration and tube formation in vitro, and increased scarring with decreased angiogenesis in vivo after myocardial infarct. This study underscores the importance of SGK1 signalling in cardiac neo-angiogenesis and wound healing after an ischemic insult in vivo.http://europepmc.org/articles/PMC3827188?pdf=render
spellingShingle Elham Zarrinpashneh
Tommaso Poggioli
Padmini Sarathchandra
Jonas Lexow
Laurent Monassier
Cesare Terracciano
Florian Lang
Federico Damilano
Jessica Q Zhou
Anthony Rosenzweig
Nadia Rosenthal
Maria Paola Santini
Ablation of SGK1 impairs endothelial cell migration and tube formation leading to decreased neo-angiogenesis following myocardial infarction.
PLoS ONE
title Ablation of SGK1 impairs endothelial cell migration and tube formation leading to decreased neo-angiogenesis following myocardial infarction.
title_full Ablation of SGK1 impairs endothelial cell migration and tube formation leading to decreased neo-angiogenesis following myocardial infarction.
title_fullStr Ablation of SGK1 impairs endothelial cell migration and tube formation leading to decreased neo-angiogenesis following myocardial infarction.
title_full_unstemmed Ablation of SGK1 impairs endothelial cell migration and tube formation leading to decreased neo-angiogenesis following myocardial infarction.
title_short Ablation of SGK1 impairs endothelial cell migration and tube formation leading to decreased neo-angiogenesis following myocardial infarction.
title_sort ablation of sgk1 impairs endothelial cell migration and tube formation leading to decreased neo angiogenesis following myocardial infarction
url http://europepmc.org/articles/PMC3827188?pdf=render
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