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Nkx2.5 insufficiency leads to atrial electrical remodeling through Wnt signaling in HL-1 cells

Homeobox protein Nxk-2.5 (Nkx2.5) is a homeobox transcription factor that promotes chamber-like myocardial gene expression. Data from a previous genome-wide association study suggested that Nkx2.5 may be associated with the genetic variation that underlies atrial fibrillation (AF). Nkx2.5 loss of fu...

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Autores principales: Chen, Jingjing, Xu, Shunen, Li, Wei, Wu, Lirong, Wang, Long, Li, Yongkang, Zhou, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6880433/
https://www.ncbi.nlm.nih.gov/pubmed/31798700
http://dx.doi.org/10.3892/etm.2019.8134
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author Chen, Jingjing
Xu, Shunen
Li, Wei
Wu, Lirong
Wang, Long
Li, Yongkang
Zhou, Wei
author_facet Chen, Jingjing
Xu, Shunen
Li, Wei
Wu, Lirong
Wang, Long
Li, Yongkang
Zhou, Wei
author_sort Chen, Jingjing
collection PubMed
description Homeobox protein Nxk-2.5 (Nkx2.5) is a homeobox transcription factor that promotes chamber-like myocardial gene expression. Data from a previous genome-wide association study suggested that Nkx2.5 may be associated with the genetic variation that underlies atrial fibrillation (AF). Nkx2.5 loss of function has been demonstrated to be associated with an increasing susceptibility of familial AF. Therefore, the aim of the present study was to investigate the effect of Nkx2.5 loss of function on electrophysiological substrates in HL-1 cells. To the best of our knowledge, the results demonstrated for the first time that Nkx2.5 expression was significantly decreased in a rat model exhibiting AF. The effect of silencing Nkx2.5 was assessed following transfection with adenoviral vectors with specific NKX2.5-shRNA. The effect of Nkx2.5 silencing on potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4), gap junction alpha-5 protein (Cx40), calcium handling proteins and protein Wnt-11 (Wnt11) expression levels was also assessed in HL-1 cells. The results revealed that Nkx2.5 silencing increased HCN4 expression, decreased Cx40 expression and disrupted the expression of calcium handling proteins. Additionally, Wnt11 signal protein expression was decreased following Nkx2.5 silencing. The results of the present study demonstrated that Nkx2.5 served as a transcriptional regulator of the electrophysiological substrates associated with AF.
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spelling pubmed-68804332019-12-03 Nkx2.5 insufficiency leads to atrial electrical remodeling through Wnt signaling in HL-1 cells Chen, Jingjing Xu, Shunen Li, Wei Wu, Lirong Wang, Long Li, Yongkang Zhou, Wei Exp Ther Med Articles Homeobox protein Nxk-2.5 (Nkx2.5) is a homeobox transcription factor that promotes chamber-like myocardial gene expression. Data from a previous genome-wide association study suggested that Nkx2.5 may be associated with the genetic variation that underlies atrial fibrillation (AF). Nkx2.5 loss of function has been demonstrated to be associated with an increasing susceptibility of familial AF. Therefore, the aim of the present study was to investigate the effect of Nkx2.5 loss of function on electrophysiological substrates in HL-1 cells. To the best of our knowledge, the results demonstrated for the first time that Nkx2.5 expression was significantly decreased in a rat model exhibiting AF. The effect of silencing Nkx2.5 was assessed following transfection with adenoviral vectors with specific NKX2.5-shRNA. The effect of Nkx2.5 silencing on potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4), gap junction alpha-5 protein (Cx40), calcium handling proteins and protein Wnt-11 (Wnt11) expression levels was also assessed in HL-1 cells. The results revealed that Nkx2.5 silencing increased HCN4 expression, decreased Cx40 expression and disrupted the expression of calcium handling proteins. Additionally, Wnt11 signal protein expression was decreased following Nkx2.5 silencing. The results of the present study demonstrated that Nkx2.5 served as a transcriptional regulator of the electrophysiological substrates associated with AF. D.A. Spandidos 2019-12 2019-10-25 /pmc/articles/PMC6880433/ /pubmed/31798700 http://dx.doi.org/10.3892/etm.2019.8134 Text en Copyright: © Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Chen, Jingjing
Xu, Shunen
Li, Wei
Wu, Lirong
Wang, Long
Li, Yongkang
Zhou, Wei
Nkx2.5 insufficiency leads to atrial electrical remodeling through Wnt signaling in HL-1 cells
title Nkx2.5 insufficiency leads to atrial electrical remodeling through Wnt signaling in HL-1 cells
title_full Nkx2.5 insufficiency leads to atrial electrical remodeling through Wnt signaling in HL-1 cells
title_fullStr Nkx2.5 insufficiency leads to atrial electrical remodeling through Wnt signaling in HL-1 cells
title_full_unstemmed Nkx2.5 insufficiency leads to atrial electrical remodeling through Wnt signaling in HL-1 cells
title_short Nkx2.5 insufficiency leads to atrial electrical remodeling through Wnt signaling in HL-1 cells
title_sort nkx2.5 insufficiency leads to atrial electrical remodeling through wnt signaling in hl-1 cells
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6880433/
https://www.ncbi.nlm.nih.gov/pubmed/31798700
http://dx.doi.org/10.3892/etm.2019.8134
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