Smad4 regulates the nuclear translocation of Nkx2-5 in cardiac differentiation

Abstract Bmp plays an important role in cardiomyocyte differentiation, but the function of Smad4 in Bmp signaling remains elusive. Here, we show that disruption of the Smad4 gene in cardiac progenitors expressing Sfrp5 led to embryonic lethality with hypoplastic heart formation. Although the express...

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Autores principales:	Wenyu Hu, Anqi Dong, Kohei Karasaki, Shota Sogabe, Daiki Okamoto, Masato Saigo, Mari Ishida, Masao Yoshizumi, Hiroki Kokubo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/facdf754252742c58ba07118dc45ac9e
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spelling	oai:doaj.org-article:facdf754252742c58ba07118dc45ac9e2021-12-02T12:09:45ZSmad4 regulates the nuclear translocation of Nkx2-5 in cardiac differentiation10.1038/s41598-021-82954-22045-2322https://doaj.org/article/facdf754252742c58ba07118dc45ac9e2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82954-2https://doaj.org/toc/2045-2322Abstract Bmp plays an important role in cardiomyocyte differentiation, but the function of Smad4 in Bmp signaling remains elusive. Here, we show that disruption of the Smad4 gene in cardiac progenitors expressing Sfrp5 led to embryonic lethality with hypoplastic heart formation. Although the expression of Nkx2-5 is regulated by Bmp signaling, expression of Nkx2-5 was weakly detected in the mutant heart. However, the nuclear translocation of Nkx2-5 was impaired. Expression of CK2 or PP1, which could alter the phosphorylation status of the NLS of Nkx2-5, was not affected, but Nkx2-5 was found to bind to Smad4 by co-immunoprecipitation experiments. Introduction of Smad4 into cells derived from Smad4 conditional knockout embryonic hearts restored the nuclear localization of Nkx2-5, and exogenous Nkx2-5 failed to translocate into the nucleus of Smad4-depleted fibroblasts. These results suggest that Smad4 plays an essential role in cardiomyocyte differentiation by controlling not only transcription but also the nuclear localization of Nkx2-5.Wenyu HuAnqi DongKohei KarasakiShota SogabeDaiki OkamotoMasato SaigoMari IshidaMasao YoshizumiHiroki KokuboNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wenyu Hu Anqi Dong Kohei Karasaki Shota Sogabe Daiki Okamoto Masato Saigo Mari Ishida Masao Yoshizumi Hiroki Kokubo Smad4 regulates the nuclear translocation of Nkx2-5 in cardiac differentiation
description	Abstract Bmp plays an important role in cardiomyocyte differentiation, but the function of Smad4 in Bmp signaling remains elusive. Here, we show that disruption of the Smad4 gene in cardiac progenitors expressing Sfrp5 led to embryonic lethality with hypoplastic heart formation. Although the expression of Nkx2-5 is regulated by Bmp signaling, expression of Nkx2-5 was weakly detected in the mutant heart. However, the nuclear translocation of Nkx2-5 was impaired. Expression of CK2 or PP1, which could alter the phosphorylation status of the NLS of Nkx2-5, was not affected, but Nkx2-5 was found to bind to Smad4 by co-immunoprecipitation experiments. Introduction of Smad4 into cells derived from Smad4 conditional knockout embryonic hearts restored the nuclear localization of Nkx2-5, and exogenous Nkx2-5 failed to translocate into the nucleus of Smad4-depleted fibroblasts. These results suggest that Smad4 plays an essential role in cardiomyocyte differentiation by controlling not only transcription but also the nuclear localization of Nkx2-5.
format	article
author	Wenyu Hu Anqi Dong Kohei Karasaki Shota Sogabe Daiki Okamoto Masato Saigo Mari Ishida Masao Yoshizumi Hiroki Kokubo
author_facet	Wenyu Hu Anqi Dong Kohei Karasaki Shota Sogabe Daiki Okamoto Masato Saigo Mari Ishida Masao Yoshizumi Hiroki Kokubo
author_sort	Wenyu Hu
title	Smad4 regulates the nuclear translocation of Nkx2-5 in cardiac differentiation
title_short	Smad4 regulates the nuclear translocation of Nkx2-5 in cardiac differentiation
title_full	Smad4 regulates the nuclear translocation of Nkx2-5 in cardiac differentiation
title_fullStr	Smad4 regulates the nuclear translocation of Nkx2-5 in cardiac differentiation
title_full_unstemmed	Smad4 regulates the nuclear translocation of Nkx2-5 in cardiac differentiation
title_sort	smad4 regulates the nuclear translocation of nkx2-5 in cardiac differentiation
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/facdf754252742c58ba07118dc45ac9e
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Smad4 regulates the nuclear translocation of Nkx2-5 in cardiac differentiation

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