Targeting GATA4 for cardiac repair

Abstract

Various strategies have been applied to replace the loss of cardiomyocytes in order to restore reduced cardiac function and prevent the progression of heart disease. Intensive research efforts in the field of cellular reprogramming and cell transplantation may eventually lead to efficient in vivo applications for the treatment of cardiac injuries, representing a novel treatment strategy for regenerative medicine. Modulation of cardiac transcription factor (TF) networks by chemical entities represents another viable option for therapeutic interventions. Comprehensive screening projects have revealed a number of molecular entities acting on molecular pathways highly critical for cellular lineage commitment and differentiation, including compounds targeting Wnt‐ and transforming growth factor beta (TGFβ)‐signaling. Furthermore, previous studies have demonstrated that GATA4 and NKX2‐5 are essential TFs in gene regulation of cardiac development and hypertrophy. For example, both of these TFs are required to fully activate mechanical stretch‐responsive genes such as atrial natriuretic peptide and brain natriuretic peptide (BNP). We have previously reported that the compound 3i‐1000 efficiently inhibited the synergy of the GATA4–NKX2‐5 interaction. Cellular effects of 3i‐1000 have been further characterized in a number of confirmatory in vitro bioassays, including rat cardiac myocytes and animal models of ischemic injury and angiotensin II‐induced pressure overload, suggesting the potential for small molecule‐induced cardioprotection.

Expression Profile of Long Noncoding RNAs and Circular RNAs in Mouse C3H10T1/2 Mesenchymal Stem Cells Undergoing Myogenic and Cardiomyogenic Differentiation

“…Moreover, we noticed that the expression level of GATA4 increased more than 100 times ( ∗∗ P < 0.01) after 5-AZA treatment. GATA4 has been shown to control the differentiation and growth of many kinds of cells [ 18 , 19 ]. In the process of myocardial cell differentiation, the quantity of GATA4 transfected bone marrow MSCs was higher than that of control cells, suggesting that GATA4 increased the differentiation potential of stem cells into myocardial cells.…”

CircERBB2IP promotes post-infarction revascularization via the miR-145a-5p/Smad5 axis

“… 23 GATA4 is a transcription factor with a conserved zinc-finger domain that regulates cell differentiation and survival, promotes angiogenesis, 24 and improves the function of ischemic myocardium. 25 Bioinformatics analysis predicted that GATA4 could bind to the ERBB2IP promoter, which was confirmed by luciferase reporter gene and ChIP analysis. Subsequently, we found that overexpression of GATA4 increased the expression level of circERBB2IP, suggesting that GATA4 might promote the transcription of circERBB2IP.…”

Novel estrogen-responsive genes (ERGs) for the evaluation of estrogenic activity

“…EGR3 , known as an ERG [ 119 ], has been used for evaluation of estrogenic activity of the constituents in foods and medicines [ 120 ]. GATA4 encodes a transcription factor that binds to the GATA motif as a cis -element and transactivates the genes for various cell functions such as the development of heart, liver, lung, and urogenital cells [ 121 , 122 ]. Due to its suppressive effects against ovarian and colorectal cancer cell proliferation, GATA4 is considered to act as a potential tumor suppressor gene [ 123 , 124 ].…”