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Loss of GATA4 C-Terminus by p.S335X Mutation Modulates Coronary Artery Vascular Smooth Muscle Cell Phenotype

Authors :
Ting-Yan Yu
Xin-Xin Chen
Qing-Wen Liu
Fang-Fang Ma
Hong-Lang Huang
Lei Zhou
Wei Zhang
Source :
Mediators of Inflammation, Vol 2021 (2021)
Publication Year :
2021
Publisher :
Hindawi Limited, 2021.

Abstract

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.

Subjects

Subjects :
Pathology
RB1-214

Details

Language :
English
ISSN :
09629351 and 14661861
Volume :
2021
Database :
Directory of Open Access Journals
Journal :
Mediators of Inflammation
Publication Type :
Academic Journal
Accession number :
edsdoj.1cd4bb78d7454a4eb92b1dd6df2dfacd
Document Type :
article
Full Text :
https://doi.org/10.1155/2021/3698386