DUSP5 expression in left ventricular cardiomyocytes of young hearts regulates thyroid hormone (T3)-induced proliferative ERK1/2 signaling

Abstract Cardiomyocytes of newborn mice proliferate after injury or exposure to growth factors. However, these responses are diminished after postnatal day-6 (P6), representing a barrier to building new cardiac muscle in adults. We have previously shown that exogenous thyroid hormone (T3) stimulates...

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Autores principales:	Nikolay Bogush, Lin Tan, Hussain Naib, Ebrahim Faizullabhoy, John W. Calvert, Siiri E. Iismaa, Ankan Gupta, Ramani Ramchandran, David I. K. Martin, Robert M. Graham, Ahsan Husain, Nawazish Naqvi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fd5f777a271c4c42af5f2172602fd2f5
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spelling	oai:doaj.org-article:fd5f777a271c4c42af5f2172602fd2f52021-12-02T12:42:27ZDUSP5 expression in left ventricular cardiomyocytes of young hearts regulates thyroid hormone (T3)-induced proliferative ERK1/2 signaling10.1038/s41598-020-78825-x2045-2322https://doaj.org/article/fd5f777a271c4c42af5f2172602fd2f52020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78825-xhttps://doaj.org/toc/2045-2322Abstract Cardiomyocytes of newborn mice proliferate after injury or exposure to growth factors. However, these responses are diminished after postnatal day-6 (P6), representing a barrier to building new cardiac muscle in adults. We have previously shown that exogenous thyroid hormone (T3) stimulates cardiomyocyte proliferation in P2 cardiomyocytes, by activating insulin-like growth factor-1 receptor (IGF-1R)-mediated ERK1/2 signaling. But whether exogenous T3 functions as a mitogen in post-P6 murine hearts is not known. Here, we show that exogenous T3 increases the cardiomyocyte endowment of P8 hearts, but the proliferative response is confined to cardiomyocytes of the left ventricular (LV) apex. Exogenous T3 stimulates proliferative ERK1/2 signaling in apical cardiomyocytes, but not in those of the LV base, which is inhibited by expression of the nuclear phospho-ERK1/2-specific dual-specificity phosphatase, DUSP5. Developmentally, between P7 and P14, DUSP5 expression increases in the myocardium from the LV base to its apex; after this period, it is uniformly expressed throughout the LV. In young adult hearts, exogenous T3 increases cardiomyocyte numbers after DUSP5 depletion, which might be useful for eliciting cardiac regeneration.Nikolay BogushLin TanHussain NaibEbrahim FaizullabhoyJohn W. CalvertSiiri E. IismaaAnkan GuptaRamani RamchandranDavid I. K. MartinRobert M. GrahamAhsan HusainNawazish NaqviNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-14 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nikolay Bogush Lin Tan Hussain Naib Ebrahim Faizullabhoy John W. Calvert Siiri E. Iismaa Ankan Gupta Ramani Ramchandran David I. K. Martin Robert M. Graham Ahsan Husain Nawazish Naqvi DUSP5 expression in left ventricular cardiomyocytes of young hearts regulates thyroid hormone (T3)-induced proliferative ERK1/2 signaling
description	Abstract Cardiomyocytes of newborn mice proliferate after injury or exposure to growth factors. However, these responses are diminished after postnatal day-6 (P6), representing a barrier to building new cardiac muscle in adults. We have previously shown that exogenous thyroid hormone (T3) stimulates cardiomyocyte proliferation in P2 cardiomyocytes, by activating insulin-like growth factor-1 receptor (IGF-1R)-mediated ERK1/2 signaling. But whether exogenous T3 functions as a mitogen in post-P6 murine hearts is not known. Here, we show that exogenous T3 increases the cardiomyocyte endowment of P8 hearts, but the proliferative response is confined to cardiomyocytes of the left ventricular (LV) apex. Exogenous T3 stimulates proliferative ERK1/2 signaling in apical cardiomyocytes, but not in those of the LV base, which is inhibited by expression of the nuclear phospho-ERK1/2-specific dual-specificity phosphatase, DUSP5. Developmentally, between P7 and P14, DUSP5 expression increases in the myocardium from the LV base to its apex; after this period, it is uniformly expressed throughout the LV. In young adult hearts, exogenous T3 increases cardiomyocyte numbers after DUSP5 depletion, which might be useful for eliciting cardiac regeneration.
format	article
author	Nikolay Bogush Lin Tan Hussain Naib Ebrahim Faizullabhoy John W. Calvert Siiri E. Iismaa Ankan Gupta Ramani Ramchandran David I. K. Martin Robert M. Graham Ahsan Husain Nawazish Naqvi
author_facet	Nikolay Bogush Lin Tan Hussain Naib Ebrahim Faizullabhoy John W. Calvert Siiri E. Iismaa Ankan Gupta Ramani Ramchandran David I. K. Martin Robert M. Graham Ahsan Husain Nawazish Naqvi
author_sort	Nikolay Bogush
title	DUSP5 expression in left ventricular cardiomyocytes of young hearts regulates thyroid hormone (T3)-induced proliferative ERK1/2 signaling
title_short	DUSP5 expression in left ventricular cardiomyocytes of young hearts regulates thyroid hormone (T3)-induced proliferative ERK1/2 signaling
title_full	DUSP5 expression in left ventricular cardiomyocytes of young hearts regulates thyroid hormone (T3)-induced proliferative ERK1/2 signaling
title_fullStr	DUSP5 expression in left ventricular cardiomyocytes of young hearts regulates thyroid hormone (T3)-induced proliferative ERK1/2 signaling
title_full_unstemmed	DUSP5 expression in left ventricular cardiomyocytes of young hearts regulates thyroid hormone (T3)-induced proliferative ERK1/2 signaling
title_sort	dusp5 expression in left ventricular cardiomyocytes of young hearts regulates thyroid hormone (t3)-induced proliferative erk1/2 signaling
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/fd5f777a271c4c42af5f2172602fd2f5
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DUSP5 expression in left ventricular cardiomyocytes of young hearts regulates thyroid hormone (T3)-induced proliferative ERK1/2 signaling

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