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DACT1 Involvement in the Cytoskeletal Arrangement of Cardiomyocytes in Atrial Fibrillation by Regulating Cx43
OBJECTIVE: To determine the role of the dishevelled binding antagonist of beta catenin 1 (DACT1) in the cytoskeletal arrangement of cardiomyocytes in atrial fibrillation (AF). METHODS: The DACT1 expression and its associations with the degree of fibrosis and β-catenin in valvular disease patients we...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Sociedade Brasileira de Cirurgia Cardiovascular
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6894021/ https://www.ncbi.nlm.nih.gov/pubmed/31545578 http://dx.doi.org/10.21470/1678-9741-2019-0033 |
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author | Hou, Jian Yue, Yuan Hu, Bo Xu, Guangtao Su, Ruibing Lv, Linhua Huang, Jiaxing Yao, Jianping Guan, Yuanjun Wang, Keke Wu, Zhongkai |
author_facet | Hou, Jian Yue, Yuan Hu, Bo Xu, Guangtao Su, Ruibing Lv, Linhua Huang, Jiaxing Yao, Jianping Guan, Yuanjun Wang, Keke Wu, Zhongkai |
author_sort | Hou, Jian |
collection | PubMed |
description | OBJECTIVE: To determine the role of the dishevelled binding antagonist of beta catenin 1 (DACT1) in the cytoskeletal arrangement of cardiomyocytes in atrial fibrillation (AF). METHODS: The DACT1 expression and its associations with the degree of fibrosis and β-catenin in valvular disease patients were analyzed by immunohistochemistry and Masson’s staining. DACT1 was overexpressed in the atrial myocyte cell line (HL-1) and the cardiac cell line (H9C2) by adenoviral vectors. Alterations in the fibrous actin (F-actin) content and organization and the expression of β-catenin were detected by flow cytometry, immunofluorescence, and Western blotting. Additionally, the association of DACT1 with gap junctions connexin 43 (Cx43) was detected by immunohistochemistry, immunofluorescence, and Western blotting. RESULTS: Decreased cytoplasmic DACT1 expression in the myocardium was associated with AF (P=0.037) and a high degree of fibrosis (weak vs. strong, P=0.028; weak vs. very strong, P=0.029). A positive association was observed between DACT1 and β-catenin expression in clinical samples (P=0.028, Spearman’s rho=0.408). Furthermore, overexpression of DACT1 in HL-1 and H9C2 cells induced an increase in β-catenin and subsequent partial colocalization of DACT1 and β-catenin. In addition, F-actin content and organization were enhanced. Interestingly, DACT1 was positively correlated with the Cx43 expression in clinical samples (P=0.048, Spearman’s rho=0.370) and changed the Cx43 distribution in cardiac cell lines. CONCLUSION: DACT1 proved to be a novel AF-related gene by regulating Cx43 via cytoskeletal organization induced by β-catenin accumulation in cardiomyocytes. DACT1 could thus serve as a potential therapeutic marker for AF. |
format | Online Article Text |
id | pubmed-6894021 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Sociedade Brasileira de Cirurgia Cardiovascular |
record_format | MEDLINE/PubMed |
spelling | pubmed-68940212019-12-10 DACT1 Involvement in the Cytoskeletal Arrangement of Cardiomyocytes in Atrial Fibrillation by Regulating Cx43 Hou, Jian Yue, Yuan Hu, Bo Xu, Guangtao Su, Ruibing Lv, Linhua Huang, Jiaxing Yao, Jianping Guan, Yuanjun Wang, Keke Wu, Zhongkai Braz J Cardiovasc Surg Original Article OBJECTIVE: To determine the role of the dishevelled binding antagonist of beta catenin 1 (DACT1) in the cytoskeletal arrangement of cardiomyocytes in atrial fibrillation (AF). METHODS: The DACT1 expression and its associations with the degree of fibrosis and β-catenin in valvular disease patients were analyzed by immunohistochemistry and Masson’s staining. DACT1 was overexpressed in the atrial myocyte cell line (HL-1) and the cardiac cell line (H9C2) by adenoviral vectors. Alterations in the fibrous actin (F-actin) content and organization and the expression of β-catenin were detected by flow cytometry, immunofluorescence, and Western blotting. Additionally, the association of DACT1 with gap junctions connexin 43 (Cx43) was detected by immunohistochemistry, immunofluorescence, and Western blotting. RESULTS: Decreased cytoplasmic DACT1 expression in the myocardium was associated with AF (P=0.037) and a high degree of fibrosis (weak vs. strong, P=0.028; weak vs. very strong, P=0.029). A positive association was observed between DACT1 and β-catenin expression in clinical samples (P=0.028, Spearman’s rho=0.408). Furthermore, overexpression of DACT1 in HL-1 and H9C2 cells induced an increase in β-catenin and subsequent partial colocalization of DACT1 and β-catenin. In addition, F-actin content and organization were enhanced. Interestingly, DACT1 was positively correlated with the Cx43 expression in clinical samples (P=0.048, Spearman’s rho=0.370) and changed the Cx43 distribution in cardiac cell lines. CONCLUSION: DACT1 proved to be a novel AF-related gene by regulating Cx43 via cytoskeletal organization induced by β-catenin accumulation in cardiomyocytes. DACT1 could thus serve as a potential therapeutic marker for AF. Sociedade Brasileira de Cirurgia Cardiovascular 2019 /pmc/articles/PMC6894021/ /pubmed/31545578 http://dx.doi.org/10.21470/1678-9741-2019-0033 Text en http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Hou, Jian Yue, Yuan Hu, Bo Xu, Guangtao Su, Ruibing Lv, Linhua Huang, Jiaxing Yao, Jianping Guan, Yuanjun Wang, Keke Wu, Zhongkai DACT1 Involvement in the Cytoskeletal Arrangement of Cardiomyocytes in Atrial Fibrillation by Regulating Cx43 |
title | DACT1 Involvement in the Cytoskeletal Arrangement of Cardiomyocytes in Atrial Fibrillation by Regulating Cx43 |
title_full | DACT1 Involvement in the Cytoskeletal Arrangement of Cardiomyocytes in Atrial Fibrillation by Regulating Cx43 |
title_fullStr | DACT1 Involvement in the Cytoskeletal Arrangement of Cardiomyocytes in Atrial Fibrillation by Regulating Cx43 |
title_full_unstemmed | DACT1 Involvement in the Cytoskeletal Arrangement of Cardiomyocytes in Atrial Fibrillation by Regulating Cx43 |
title_short | DACT1 Involvement in the Cytoskeletal Arrangement of Cardiomyocytes in Atrial Fibrillation by Regulating Cx43 |
title_sort | dact1 involvement in the cytoskeletal arrangement of cardiomyocytes in atrial fibrillation by regulating cx43 |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6894021/ https://www.ncbi.nlm.nih.gov/pubmed/31545578 http://dx.doi.org/10.21470/1678-9741-2019-0033 |
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