Loss of GATA4 C-Terminus by p.S335X Mutation Modulates Coronary Artery Vascular Smooth Muscle Cell Phenotype
Coronary artery disease (CAD) has been the leading cause of morbidity and mortality worldwide, and its pathogenesis is closely related with the proliferation and migration of vascular smooth muscle cell (VSMC). We previously reported a truncated GATA4 protein lacking C-terminus induced by p.S335X mu...
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Wiley
2021-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2021/3698386 |
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| author | Ting-Yan Yu Xin-Xin Chen Qing-Wen Liu Fang-Fang Ma Hong-Lang Huang Lei Zhou Wei Zhang |
| author_facet | Ting-Yan Yu Xin-Xin Chen Qing-Wen Liu Fang-Fang Ma Hong-Lang Huang Lei Zhou Wei Zhang |
| author_sort | Ting-Yan Yu |
| collection | DOAJ |
| description | Coronary artery disease (CAD) has been the leading cause of morbidity and mortality worldwide, and its pathogenesis is closely related with the proliferation and migration of vascular smooth muscle cell (VSMC). We previously reported a truncated GATA4 protein lacking C-terminus induced by p.S335X mutation in cardiomyocyte from ventricular septal defect (VSD) patients. However, it is still unclear whether GATA4 p.S335X mutation could influence the development of CAD. GATA4 wild-type (WT) and p.S335X mutant (MU) overexpression plasmids were constructed and transfected transiently into rat coronary artery smooth muscle cell (RCSMC) to observe the proliferative and migratory abilities by MTS and wound healing assay, respectively. PCR array was used to preliminarily detect the expression of phenotypic modulation-related genes, and QRT-PCR was then carried out to verify the screened differentially expressed genes (DEGs). The results showed that, when stimulated by fetal bovine serum (10%) for 24 h or tumor necrosis factor-α (10 or 30 ng/ml) for 10 or 24 h, deletion of GATA4 C-terminus by p.S335X mutation in GATA4 enhanced the proliferation of RCSMC, without alteration of the migration capability. Twelve DEGs, including Fas, Hbegf, Itga5, Aimp1, Cxcl1, Il15, Il2rg, Il7, Tnfsf10, Il1r1, Irak1, and Tlr3, were screened and identified as phenotypic modulation-related genes. Our data might be beneficial for further exploration regarding the mechanisms of GATA4 p.S335X mutation on the phenotypic modulation of coronary VSMC. |
| format | Article |
| id | doaj-art-1cd4bb78d7454a4eb92b1dd6df2dfacd |
| institution | OA Journals |
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| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-1cd4bb78d7454a4eb92b1dd6df2dfacd2025-08-20T02:01:46ZengWileyMediators of Inflammation0962-93511466-18612021-01-01202110.1155/2021/36983863698386Loss of GATA4 C-Terminus by p.S335X Mutation Modulates Coronary Artery Vascular Smooth Muscle Cell PhenotypeTing-Yan Yu0Xin-Xin Chen1Qing-Wen Liu2Fang-Fang Ma3Hong-Lang Huang4Lei Zhou5Wei Zhang6Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029 Jiangsu, ChinaDepartment of Cardiology, The Affiliated Hospital of Jiangsu University, Zhenjiang, 212001 Jiangsu, ChinaDepartment of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029 Jiangsu, ChinaDepartment of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029 Jiangsu, ChinaXiamen Key Laboratory of Cardiac Electrophysiology, Xiamen Institute of Cardiovascular Diseases, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361003 Fujian, ChinaDepartment of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029 Jiangsu, ChinaXiamen Key Laboratory of Cardiac Electrophysiology, Xiamen Institute of Cardiovascular Diseases, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361003 Fujian, ChinaCoronary artery disease (CAD) has been the leading cause of morbidity and mortality worldwide, and its pathogenesis is closely related with the proliferation and migration of vascular smooth muscle cell (VSMC). We previously reported a truncated GATA4 protein lacking C-terminus induced by p.S335X mutation in cardiomyocyte from ventricular septal defect (VSD) patients. However, it is still unclear whether GATA4 p.S335X mutation could influence the development of CAD. GATA4 wild-type (WT) and p.S335X mutant (MU) overexpression plasmids were constructed and transfected transiently into rat coronary artery smooth muscle cell (RCSMC) to observe the proliferative and migratory abilities by MTS and wound healing assay, respectively. PCR array was used to preliminarily detect the expression of phenotypic modulation-related genes, and QRT-PCR was then carried out to verify the screened differentially expressed genes (DEGs). The results showed that, when stimulated by fetal bovine serum (10%) for 24 h or tumor necrosis factor-α (10 or 30 ng/ml) for 10 or 24 h, deletion of GATA4 C-terminus by p.S335X mutation in GATA4 enhanced the proliferation of RCSMC, without alteration of the migration capability. Twelve DEGs, including Fas, Hbegf, Itga5, Aimp1, Cxcl1, Il15, Il2rg, Il7, Tnfsf10, Il1r1, Irak1, and Tlr3, were screened and identified as phenotypic modulation-related genes. Our data might be beneficial for further exploration regarding the mechanisms of GATA4 p.S335X mutation on the phenotypic modulation of coronary VSMC.http://dx.doi.org/10.1155/2021/3698386 |
| spellingShingle | Ting-Yan Yu Xin-Xin Chen Qing-Wen Liu Fang-Fang Ma Hong-Lang Huang Lei Zhou Wei Zhang Loss of GATA4 C-Terminus by p.S335X Mutation Modulates Coronary Artery Vascular Smooth Muscle Cell Phenotype Mediators of Inflammation |
| title | Loss of GATA4 C-Terminus by p.S335X Mutation Modulates Coronary Artery Vascular Smooth Muscle Cell Phenotype |
| title_full | Loss of GATA4 C-Terminus by p.S335X Mutation Modulates Coronary Artery Vascular Smooth Muscle Cell Phenotype |
| title_fullStr | Loss of GATA4 C-Terminus by p.S335X Mutation Modulates Coronary Artery Vascular Smooth Muscle Cell Phenotype |
| title_full_unstemmed | Loss of GATA4 C-Terminus by p.S335X Mutation Modulates Coronary Artery Vascular Smooth Muscle Cell Phenotype |
| title_short | Loss of GATA4 C-Terminus by p.S335X Mutation Modulates Coronary Artery Vascular Smooth Muscle Cell Phenotype |
| title_sort | loss of gata4 c terminus by p s335x mutation modulates coronary artery vascular smooth muscle cell phenotype |
| url | http://dx.doi.org/10.1155/2021/3698386 |
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