Activated Met signalling in the developing mouse heart leads to cardiac disease.

<h4>Background</h4>The Hepatocyte Growth Factor (HGF) is a pleiotropic cytokine involved in many physiological processes, including skeletal muscle, placenta and liver development. Little is known about its role and that of Met tyrosine kinase receptor in cardiac development.<h4>Me...

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Autores principales:	Christian Leo, Valentina Sala, Mara Morello, Amedeo Chiribiri, Ilan Riess, Daniele Mancardi, Stefano Schiaffino, Carola Ponzetto, Tiziana Crepaldi
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ff6f1a6b6c37420facb91224cc26c823
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spelling	oai:doaj.org-article:ff6f1a6b6c37420facb91224cc26c8232021-11-18T06:59:01ZActivated Met signalling in the developing mouse heart leads to cardiac disease.1932-620310.1371/journal.pone.0014675https://doaj.org/article/ff6f1a6b6c37420facb91224cc26c8232011-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21347410/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The Hepatocyte Growth Factor (HGF) is a pleiotropic cytokine involved in many physiological processes, including skeletal muscle, placenta and liver development. Little is known about its role and that of Met tyrosine kinase receptor in cardiac development.<h4>Methodology/principal findings</h4>In this study, we generated two transgenic mice with cardiac-specific, tetracycline-suppressible expression of either Hepatocyte Growth Factor (HGF) or the constitutively activated Tpr-Met kinase to explore: i) the effect of stimulation of the endogenous Met receptor by autocrine production of HGF and ii) the consequence of sustained activation of Met signalling in the heart. We first showed that Met is present in the neonatal cardiomyocytes and is responsive to exogenous HGF. Exogenous HGF starting from prenatal stage enhanced cardiac proliferation and reduced sarcomeric proteins and Connexin43 (Cx43) in newborn mice. As adults, these transgenics developed systolic contractile dysfunction. Conversely, prenatal Tpr-Met expression was lethal after birth. Inducing Tpr-Met expression during postnatal life caused early-onset heart failure, characterized by decreased Cx43, upregulation of fetal genes and hypertrophy.<h4>Conclusions/significance</h4>Taken together, our data show that excessive activation of the HGF/Met system in development may result in cardiac damage and suggest that Met signalling may be implicated in the pathogenesis of cardiac disease.Christian LeoValentina SalaMara MorelloAmedeo ChiribiriIlan RiessDaniele MancardiStefano SchiaffinoCarola PonzettoTiziana CrepaldiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 2, p e14675 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Christian Leo Valentina Sala Mara Morello Amedeo Chiribiri Ilan Riess Daniele Mancardi Stefano Schiaffino Carola Ponzetto Tiziana Crepaldi Activated Met signalling in the developing mouse heart leads to cardiac disease.
description	<h4>Background</h4>The Hepatocyte Growth Factor (HGF) is a pleiotropic cytokine involved in many physiological processes, including skeletal muscle, placenta and liver development. Little is known about its role and that of Met tyrosine kinase receptor in cardiac development.<h4>Methodology/principal findings</h4>In this study, we generated two transgenic mice with cardiac-specific, tetracycline-suppressible expression of either Hepatocyte Growth Factor (HGF) or the constitutively activated Tpr-Met kinase to explore: i) the effect of stimulation of the endogenous Met receptor by autocrine production of HGF and ii) the consequence of sustained activation of Met signalling in the heart. We first showed that Met is present in the neonatal cardiomyocytes and is responsive to exogenous HGF. Exogenous HGF starting from prenatal stage enhanced cardiac proliferation and reduced sarcomeric proteins and Connexin43 (Cx43) in newborn mice. As adults, these transgenics developed systolic contractile dysfunction. Conversely, prenatal Tpr-Met expression was lethal after birth. Inducing Tpr-Met expression during postnatal life caused early-onset heart failure, characterized by decreased Cx43, upregulation of fetal genes and hypertrophy.<h4>Conclusions/significance</h4>Taken together, our data show that excessive activation of the HGF/Met system in development may result in cardiac damage and suggest that Met signalling may be implicated in the pathogenesis of cardiac disease.
format	article
author	Christian Leo Valentina Sala Mara Morello Amedeo Chiribiri Ilan Riess Daniele Mancardi Stefano Schiaffino Carola Ponzetto Tiziana Crepaldi
author_facet	Christian Leo Valentina Sala Mara Morello Amedeo Chiribiri Ilan Riess Daniele Mancardi Stefano Schiaffino Carola Ponzetto Tiziana Crepaldi
author_sort	Christian Leo
title	Activated Met signalling in the developing mouse heart leads to cardiac disease.
title_short	Activated Met signalling in the developing mouse heart leads to cardiac disease.
title_full	Activated Met signalling in the developing mouse heart leads to cardiac disease.
title_fullStr	Activated Met signalling in the developing mouse heart leads to cardiac disease.
title_full_unstemmed	Activated Met signalling in the developing mouse heart leads to cardiac disease.
title_sort	activated met signalling in the developing mouse heart leads to cardiac disease.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/ff6f1a6b6c37420facb91224cc26c823
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Activated Met signalling in the developing mouse heart leads to cardiac disease.

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