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Molecular adaptations to endurance exercise and skeletal muscle fibre plasticity
Published in Adam P. Sharples, James P. Morton, Henning Wackerhage, Molecular Exercise Physiology, 2022
Unlike in an athlete, the signals for pathological hypertrophy of the heart are derived from chronic changes (e.g. from the elevation of blood pressure, loss of blood flow, genetic mutations) resulting in an increase in wall thickness, chamber volume and collagen that lead to a decrease in ejection fraction (Figure 9.1). In arguably the first landmark paper on the molecular mechanism underlying hypertrophic cardiomyopathy, Eric Olson and his team identified two transcription factors, NFAT (nuclear factors of activated T cells) and GATA-4 (GATA binding protein 4), that could bind to the promoter of genes that were upregulated in pathologic cardiac hypertrophy (27). NFATs were interesting because they are regulated by the Ca2+-activated phosphatase, calcineurin. When calcineurin is active, it dephosphorylates the NFATs, they move to the nucleus and together with GATA-4 change gene expression and potentially drive cardiac hypertrophy.
GATA2 Deficiency
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Located on chromosome 3q21.3, the guanine-adenine-thymine-adenine 2 (GATA2) gene spans 13.7 kb with seven exons (including two untranslated 5-prime exons) and encodes a 480 aa, 50 kDa protein (GATA2 or GATA binding protein 2), which constitutes one of six GATA transcription factors in humans (i.e., GATA1–6), with GATA1–3 largely expressed in hematopoietic cells, while GATA4–6 is often expressed in nonhematopoietic tissues such as heart and gut. Specifically, GATA-2 predominantly occurs in adult and developing HSC, myeloid progenitors and mast cells, and represents a pivotal regulator of HSC and their progeny, hematopoietic progenitor cells (HPC). By contrast, GATA-1 often targets erythroid cells, megakaryocytes, and eosinophils, and GATA3 affects T cells [11].
Healing the Heart with Whole Foods and Food Bioactives
Published in Stephen T. Sinatra, Mark C. Houston, Nutritional and Integrative Strategies in Cardiovascular Medicine, 2015
From a nutrigenomic perspective, an animal study by Collison et al.149 demonstrated that an iTFA-containing diet induced over twice as many cardiac differentially expressed genes (DEGs) in males compared to females, including downregulation of Gata4, Mef2d, and Srebf2. This type of nutrigenomic research needs to be evaluated in human clinical trials as this information would be invaluable for making dietary recommendations and improving patient compliance to eating regimens.
Reg3β: A Potential Therapeutic Target for Tissue Injury and Inflammation-Associated Disorders
Published in International Reviews of Immunology, 2022
Yuwen Cao, Yu Tian, Yueqin Liu, Zhaoliang Su
Emerging studies have focused on Reg3β-related molecules to further understand the functions and molecular mechanisms of Reg3β. GATA4 is identified as a transcriptional activator or repressor of Reg3β gene activity in the intestinal epithelium. It contains two conserved zinc finger domains and a C-terminal nuclear localization sequence as well as two N-terminal transcriptional activation domains [36]. Several endodermal tissues, such as pancreas, liver, kidney, heart, and intestine, express GATA4 [37]. GATA4 depletion identifies Reg3β as a putative GATA4 gene target by using an unbiased approach to gene expression profiling in intestinal epithelial cells. Co-transfection and RNA interference assays identified the complex roles of GATA4 in controlling Reg3β expression. Through the C-terminal zinc finger domain, GATA4, functionally in combination with Cdx2, regulates the rat Reg3β gene promoter. However, GATA4 interaction with FOG1 through the GATA4 N-terminal zinc finger domain represses the GATA4/Cdx2-dependent synergistic induction of Reg3β transcription. In vivo, GATA4 intestinal epithelial conditional knockout mice support the transcriptional regulation of Reg3β [38]. GATA6 is also expressed in several endodermal tissues [39]. GATA6 and GATA4 have overlapping functions in regulating crypt cell proliferation, secretory cell differentiation, and absorptive enterocyte gene expression [40]. GATA6 is identified as a transcriptional activator of Reg4 in colon cancer cells, and the GATA6/Reg4 pathway is essential for colorectal tumorigenesis. It remains unclear whether Reg3β is a transcriptional target of GATA6 [41].
In vitro differentiation of progenitor cells isolated from juvenile pig hearts – expression of relevant gene and protein markers
Published in Scandinavian Cardiovascular Journal, 2018
Simon Limbrecht Mogensen, Martin Krøyer Rasmussen, Niels Oksbjerg, Jette Feveile Young, Jens Rolighed Larsen
The heart is one of the earliest organs to form and to produce specific gene transcripts, including those of Nkx-2.5, and GATA-4, during the embryonic stages [24–26]. GATA-4 is one of the transcription factors that is expressed earliest in the heart, and it regulates the expression of specific genes during morphogenesis [25,27]. GATA-4 has therefore been utilized as a marker of early cardiac commitment by differentiating CPCs [15,17]. We observed GATA-4 mRNA expression during both the proliferation and differentiation of the isolated cells. Unexpectedly, we observed a significant decrease in its expression level at the initiation of differentiation. The down regulation of GATA-4 expression has previously been associated with insufficient cardiomyocyte differentiation as well as cardiac malformations [28,29]. Furthermore, the expression of the alpha myosin heavy chain and the troponins is affected by the level of GATA-4 expression, which activates their enhancers and promoters to allow protein expression during cardiogenesis [30]. The significant decrease in GATA-4 expression in the isolated cells could therefore underlie the stagnation in MYH7 and TNNI3 expression and their consequent insufficient differentiation.
Induction of developmental toxicity and cardiotoxicity in zebrafish embryos/larvae by acetyl-11-keto-β-boswellic acid (AKBA) through oxidative stress
Published in Drug and Chemical Toxicology, 2022
Liwen Han, Qing Xia, Lei Zhang, Xuanming Zhang, Xiaobin Li, Shanshan Zhang, Lizhen Wang, Changxiao Liu, Kechun Liu
Nkx2.5 plays an important role in cardiac morphogenesis. Gata4 is a key factor controlling heart tube formation. The significant reduction of gene expression of Nkx2.5 and Gata4 proved that cardiac progenitor gene deficiency may be associated with AKBA induced cardiotoxicity. However, this small piece of work is far from understanding the much big toxicology profile of AKBA. Much more work needs to be done including using different animal model, more systemic examinations.