Identification of a novel modulator of thyroid hormone receptor-mediated action.

<h4>Background</h4>Diabetes is characterized by reduced thyroid function and altered myogenesis after muscle injury. Here we identify a novel component of thyroid hormone action that is repressed in diabetic rat muscle.<h4>Methodology/principal findings</h4>We have identified...

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Autores principales:	Bernhard G Baumgartner, Meritxell Orpinell, Jordi Duran, Vicent Ribas, Hans E Burghardt, Daniel Bach, Ana Victoria Villar, José C Paz, Meritxell González, Marta Camps, Josep Oriola, Francisca Rivera, Manuel Palacín, Antonio Zorzano
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2007
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/68833525bbf448c3995970392406d87d
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spelling	oai:doaj.org-article:68833525bbf448c3995970392406d87d2021-11-25T06:13:52ZIdentification of a novel modulator of thyroid hormone receptor-mediated action.1932-620310.1371/journal.pone.0001183https://doaj.org/article/68833525bbf448c3995970392406d87d2007-11-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0001183https://doaj.org/toc/1932-6203<h4>Background</h4>Diabetes is characterized by reduced thyroid function and altered myogenesis after muscle injury. Here we identify a novel component of thyroid hormone action that is repressed in diabetic rat muscle.<h4>Methodology/principal findings</h4>We have identified a gene, named DOR, abundantly expressed in insulin-sensitive tissues such as skeletal muscle and heart, whose expression is highly repressed in muscle from obese diabetic rats. DOR expression is up-regulated during muscle differentiation and its loss-of-function has a negative impact on gene expression programmes linked to myogenesis or driven by thyroid hormones. In agreement with this, DOR enhances the transcriptional activity of the thyroid hormone receptor TR(alpha1). This function is driven by the N-terminal part of the protein. Moreover, DOR physically interacts with TR( alpha1) and to T(3)-responsive promoters, as shown by ChIP assays. T(3) stimulation also promotes the mobilization of DOR from its localization in nuclear PML bodies, thereby indicating that its nuclear localization and cellular function may be related.<h4>Conclusions/significance</h4>Our data indicate that DOR modulates thyroid hormone function and controls myogenesis. DOR expression is down-regulated in skeletal muscle in diabetes. This finding may be of relevance for the alterations in muscle function associated with this disease.Bernhard G BaumgartnerMeritxell OrpinellJordi DuranVicent RibasHans E BurghardtDaniel BachAna Victoria VillarJosé C PazMeritxell GonzálezMarta CampsJosep OriolaFrancisca RiveraManuel PalacínAntonio ZorzanoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 2, Iss 11, p e1183 (2007)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bernhard G Baumgartner Meritxell Orpinell Jordi Duran Vicent Ribas Hans E Burghardt Daniel Bach Ana Victoria Villar José C Paz Meritxell González Marta Camps Josep Oriola Francisca Rivera Manuel Palacín Antonio Zorzano Identification of a novel modulator of thyroid hormone receptor-mediated action.
description	<h4>Background</h4>Diabetes is characterized by reduced thyroid function and altered myogenesis after muscle injury. Here we identify a novel component of thyroid hormone action that is repressed in diabetic rat muscle.<h4>Methodology/principal findings</h4>We have identified a gene, named DOR, abundantly expressed in insulin-sensitive tissues such as skeletal muscle and heart, whose expression is highly repressed in muscle from obese diabetic rats. DOR expression is up-regulated during muscle differentiation and its loss-of-function has a negative impact on gene expression programmes linked to myogenesis or driven by thyroid hormones. In agreement with this, DOR enhances the transcriptional activity of the thyroid hormone receptor TR(alpha1). This function is driven by the N-terminal part of the protein. Moreover, DOR physically interacts with TR( alpha1) and to T(3)-responsive promoters, as shown by ChIP assays. T(3) stimulation also promotes the mobilization of DOR from its localization in nuclear PML bodies, thereby indicating that its nuclear localization and cellular function may be related.<h4>Conclusions/significance</h4>Our data indicate that DOR modulates thyroid hormone function and controls myogenesis. DOR expression is down-regulated in skeletal muscle in diabetes. This finding may be of relevance for the alterations in muscle function associated with this disease.
format	article
author	Bernhard G Baumgartner Meritxell Orpinell Jordi Duran Vicent Ribas Hans E Burghardt Daniel Bach Ana Victoria Villar José C Paz Meritxell González Marta Camps Josep Oriola Francisca Rivera Manuel Palacín Antonio Zorzano
author_facet	Bernhard G Baumgartner Meritxell Orpinell Jordi Duran Vicent Ribas Hans E Burghardt Daniel Bach Ana Victoria Villar José C Paz Meritxell González Marta Camps Josep Oriola Francisca Rivera Manuel Palacín Antonio Zorzano
author_sort	Bernhard G Baumgartner
title	Identification of a novel modulator of thyroid hormone receptor-mediated action.
title_short	Identification of a novel modulator of thyroid hormone receptor-mediated action.
title_full	Identification of a novel modulator of thyroid hormone receptor-mediated action.
title_fullStr	Identification of a novel modulator of thyroid hormone receptor-mediated action.
title_full_unstemmed	Identification of a novel modulator of thyroid hormone receptor-mediated action.
title_sort	identification of a novel modulator of thyroid hormone receptor-mediated action.
publisher	Public Library of Science (PLoS)
publishDate	2007
url	https://doaj.org/article/68833525bbf448c3995970392406d87d
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Identification of a novel modulator of thyroid hormone receptor-mediated action.

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