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Thyroid hormones inhibit TGF-¿ signaling and attenuate fibrotic responses

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Alonso Merino, Elvira & Martín Orozco, Rosa & Ruíz Llorente, Lidia & Martínez Iglesias, Olaia A. & Velasco Martín, Juan Pedro & Montero Pedrazuela, Ana & Fanjul Rodríguez, Luisa & Contreras Jurado, Silvia Constanza & Regadera, Javier & Aranda, Ana .Thyroid hormones inhibit TGF-¿ signaling and attenuate fibrotic responses.

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Alonso Merino, Elvira & Martín Orozco, Rosa & Ruíz Llorente, Lidia & Martínez Iglesias, Olaia A. & Velasco Martín, Juan Pedro & Montero Pedrazuela, Ana & Fanjul Rodríguez, Luisa & Contreras Jurado, Silvia Constanza & Regadera, Javier & Aranda, Ana. Thyroid hormones inhibit TGF-¿ signaling and attenuate fibrotic responses.

https://hdl.handle.net/20.500.12080/26186
dc.contributor.author Alonso Merino, Elvira
dc.contributor.author Martín Orozco, Rosa
dc.contributor.author Ruíz Llorente, Lidia
dc.contributor.author Martínez Iglesias, Olaia A.
dc.contributor.author Velasco Martín, Juan Pedro
dc.contributor.author Montero Pedrazuela, Ana
dc.contributor.author Fanjul Rodríguez, Luisa
dc.contributor.author Contreras Jurado, Silvia Constanza
dc.contributor.author Regadera, Javier
dc.contributor.author Aranda, Ana
dc.date.accessioned 2021-11-10T16:47:01Z
dc.date.available 2021-11-10T16:47:01Z
dc.date.created 2016-05-31
dc.identifier.uri https://hdl.handle.net/20.500.12080/26186
dc.description.abstract TGF-¿, the most potent profibrogenic factor, acts by activating SMAD (mothers against decapentaplegic) transcription factors, which bind to SMAD-binding elements in target genes. Here, we show that the thyroid hormone triiodothyronine (T3), through binding to its nuclear receptors (TRs), is able to antagonize tran scriptional activation by TGF-¿/SMAD. This antagonism involves reduced phosphorylation of SMADs and a direct interaction of the receptors with SMAD3 and SMAD4 that is independent of T3-mediated transcriptional activity but requires residues in the receptor DNA binding domain. T3 reduces occupancy of SMAD binding elements in response to TGF-¿, reducing histone acetylation and inhibiting transcription. In agreement with this transcriptional cross-talk, T3 is able to antagonize fibrotic processes in vivo. Liver fibrosis induced by carbon tetrachloride is attenuated by thyroid hormone administration to mice, whereas aged TR knockout mice spontaneously accumulate collagen. Furthermore, skin fibrosis in duced by bleomycin administration is also reduced by the thyroid hormones. These findings define an important function of the thyroid hormone receptors and suggest TR ligands could have beneficial effects to block the progression of fibrotic diseases es_ES
dc.format application/pdf es_ES
dc.language eng es_ES
dc.rights CC-BY es_ES
dc.rights.uri http://creativecommons.org/licenses/by/4.0/deed.es es_ES
dc.title Thyroid hormones inhibit TGF-¿ signaling and attenuate fibrotic responses es_ES
dc.type info:eu-repo/semantics/article es_ES
dc.rights.accessrights info:eu-repo/semantics/openAccess es_ES
dc.identifier.location N/A es_ES


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