STARS is essential to maintain cardiac development and function in vivo via a SRF pathway.

<h4>Background</h4>STARS (STriated muscle Activator of Rho Signaling) is a sarcomeric protein expressed early in cardiac development that acts as an acute stress sensor for pathological remodeling. However the role of STARS in cardiac development and function is incompletely understood....

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Autores principales:	Nelson W Chong, Andrea L Koekemoer, Samir Ounzain, Nilesh J Samani, Jordan T Shin, Stanley Y Shaw
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5ca74fa7ae754439ba213b105f25620f
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spelling	oai:doaj.org-article:5ca74fa7ae754439ba213b105f25620f2021-11-18T07:12:00ZSTARS is essential to maintain cardiac development and function in vivo via a SRF pathway.1932-620310.1371/journal.pone.0040966https://doaj.org/article/5ca74fa7ae754439ba213b105f25620f2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22815879/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>STARS (STriated muscle Activator of Rho Signaling) is a sarcomeric protein expressed early in cardiac development that acts as an acute stress sensor for pathological remodeling. However the role of STARS in cardiac development and function is incompletely understood. Here, we investigated the role of STARS in heart development and function in the zebrafish model and in vitro.<h4>Methodology and principal findings</h4>Expression of zebrafish STARS (zSTARS) first occurs in the somites by the 16 somite stage [17 hours post fertilization (hpf)]. zSTARS is expressed in both chambers of the heart by 48 hpf, and also in the developing brain, jaw structures and pectoral fins. Morpholino-induced knockdown of zSTARS alters atrial and ventricular dimensions and decreases ventricular fractional shortening (measured by high-speed video microscopy), with pericardial edema and decreased or absent circulation [abnormal cardiac phenotypes in 126/164 (77%) of morpholino-injected embryos vs. 0/152 (0%) of control morpholino embryos]. Co-injection of zsrf (serum response factor) mRNA rescues the cardiac phenotype of zSTARS knockdown, resulting in improved fractional shortening and ventricular end-diastolic dimensions. Ectopic over-expression of STARS in vitro activates the STARS proximal promoter, which contains a conserved SRF site. Chromatin immunoprecipitation demonstrates that SRF binds to this site in vivo and the SRF inhibitor CCG-1423 completely blocks STARS proximal reporter activity in H9c2 cells.<h4>Conclusions/significance</h4>This study demonstrates for the first time that STARS deficiency severely disrupts cardiac development and function in vivo and revealed a novel STARS-SRF feed-forward autoregulatory loop that could play an essential role in STARS regulation and cardiac function.Nelson W ChongAndrea L KoekemoerSamir OunzainNilesh J SamaniJordan T ShinStanley Y ShawPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 7, p e40966 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nelson W Chong Andrea L Koekemoer Samir Ounzain Nilesh J Samani Jordan T Shin Stanley Y Shaw STARS is essential to maintain cardiac development and function in vivo via a SRF pathway.
description	<h4>Background</h4>STARS (STriated muscle Activator of Rho Signaling) is a sarcomeric protein expressed early in cardiac development that acts as an acute stress sensor for pathological remodeling. However the role of STARS in cardiac development and function is incompletely understood. Here, we investigated the role of STARS in heart development and function in the zebrafish model and in vitro.<h4>Methodology and principal findings</h4>Expression of zebrafish STARS (zSTARS) first occurs in the somites by the 16 somite stage [17 hours post fertilization (hpf)]. zSTARS is expressed in both chambers of the heart by 48 hpf, and also in the developing brain, jaw structures and pectoral fins. Morpholino-induced knockdown of zSTARS alters atrial and ventricular dimensions and decreases ventricular fractional shortening (measured by high-speed video microscopy), with pericardial edema and decreased or absent circulation [abnormal cardiac phenotypes in 126/164 (77%) of morpholino-injected embryos vs. 0/152 (0%) of control morpholino embryos]. Co-injection of zsrf (serum response factor) mRNA rescues the cardiac phenotype of zSTARS knockdown, resulting in improved fractional shortening and ventricular end-diastolic dimensions. Ectopic over-expression of STARS in vitro activates the STARS proximal promoter, which contains a conserved SRF site. Chromatin immunoprecipitation demonstrates that SRF binds to this site in vivo and the SRF inhibitor CCG-1423 completely blocks STARS proximal reporter activity in H9c2 cells.<h4>Conclusions/significance</h4>This study demonstrates for the first time that STARS deficiency severely disrupts cardiac development and function in vivo and revealed a novel STARS-SRF feed-forward autoregulatory loop that could play an essential role in STARS regulation and cardiac function.
format	article
author	Nelson W Chong Andrea L Koekemoer Samir Ounzain Nilesh J Samani Jordan T Shin Stanley Y Shaw
author_facet	Nelson W Chong Andrea L Koekemoer Samir Ounzain Nilesh J Samani Jordan T Shin Stanley Y Shaw
author_sort	Nelson W Chong
title	STARS is essential to maintain cardiac development and function in vivo via a SRF pathway.
title_short	STARS is essential to maintain cardiac development and function in vivo via a SRF pathway.
title_full	STARS is essential to maintain cardiac development and function in vivo via a SRF pathway.
title_fullStr	STARS is essential to maintain cardiac development and function in vivo via a SRF pathway.
title_full_unstemmed	STARS is essential to maintain cardiac development and function in vivo via a SRF pathway.
title_sort	stars is essential to maintain cardiac development and function in vivo via a srf pathway.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/5ca74fa7ae754439ba213b105f25620f
work_keys_str_mv	AT nelsonwchong starsisessentialtomaintaincardiacdevelopmentandfunctioninvivoviaasrfpathway AT andrealkoekemoer starsisessentialtomaintaincardiacdevelopmentandfunctioninvivoviaasrfpathway AT samirounzain starsisessentialtomaintaincardiacdevelopmentandfunctioninvivoviaasrfpathway AT nileshjsamani starsisessentialtomaintaincardiacdevelopmentandfunctioninvivoviaasrfpathway AT jordantshin starsisessentialtomaintaincardiacdevelopmentandfunctioninvivoviaasrfpathway AT stanleyyshaw starsisessentialtomaintaincardiacdevelopmentandfunctioninvivoviaasrfpathway
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STARS is essential to maintain cardiac development and function in vivo via a SRF pathway.

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