CITED Proteins in the Heart of Pluripotent Cells and in Heart’s Full Potential

doi:10.20900/rmf20190005

Cited by 3 publications

(3 citation statements)

References 160 publications

(252 reference statements)

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“…Interestingly, transient exogenous WNT5A and WNT11, supplied at the 1-cell stage, efficiently rescued the viability and cardiac defects of CITED2-depleted zebrafish embryos and cardiac differentiation of mouse ESCs [ 212 ]. Dysfunctions of CITED2, a transcriptional modulator, have been widely associated with zebrafish, mouse, and human CHDs, as well as with embryonic lethality [ 55 , 212 , 213 , 214 , 215 , 216 , 217 , 218 , 219 , 220 ]. At the cellular level, CITED2 regulates the expressions of numerous genes involved in early cardiogenesis, such as BRACHYURY, MESP1, ISL1, GATA4, TBX5, MEF2C, NODAL, LEFTY1/2, PITX2C, VEGFA, WNT5A, and WNT11, among others [ 212 , 213 , 214 ].…”

Section: Harnessing Secreted Factors In Embryogenesis For Protection ...mentioning

confidence: 99%

“…Dysfunctions of CITED2, a transcriptional modulator, have been widely associated with zebrafish, mouse, and human CHDs, as well as with embryonic lethality [ 55 , 212 , 213 , 214 , 215 , 216 , 217 , 218 , 219 , 220 ]. At the cellular level, CITED2 regulates the expressions of numerous genes involved in early cardiogenesis, such as BRACHYURY, MESP1, ISL1, GATA4, TBX5, MEF2C, NODAL, LEFTY1/2, PITX2C, VEGFA, WNT5A, and WNT11, among others [ 212 , 213 , 214 ]. Thus, the supplementation of WNT5A and WNT11 at the blastocyst stage in utero holds potential for rescuing CHDs associated with CITED2 dysfunction in mammals, since the function of CITED2 is conserved across vertebrates [ 212 , 214 , 216 , 221 ].…”

Section: Harnessing Secreted Factors In Embryogenesis For Protection ...mentioning

confidence: 99%

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Charting the Path: Navigating Embryonic Development to Potentially Safeguard against Congenital Heart Defects

Bragança

Pinto

Silva

et al. 2023

JPM

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Congenital heart diseases (CHDs) are structural or functional defects present at birth due to improper heart development. Current therapeutic approaches to treating severe CHDs are primarily palliative surgical interventions during the peri- or prenatal stages, when the heart has fully developed from faulty embryogenesis. However, earlier interventions during embryonic development have the potential for better outcomes, as demonstrated by fetal cardiac interventions performed in utero, which have shown improved neonatal and prenatal survival rates, as well as reduced lifelong morbidity. Extensive research on heart development has identified key steps, cellular players, and the intricate network of signaling pathways and transcription factors governing cardiogenesis. Additionally, some reports have indicated that certain adverse genetic and environmental conditions leading to heart malformations and embryonic death may be amendable through the activation of alternative mechanisms. This review first highlights key molecular and cellular processes involved in heart development. Subsequently, it explores the potential for future therapeutic strategies, targeting early embryonic stages, to prevent CHDs, through the delivery of biomolecules or exosomes to compensate for faulty cardiogenic mechanisms. Implementing such non-surgical interventions during early gestation may offer a prophylactic approach toward reducing the occurrence and severity of CHDs.

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Section: Harnessing Secreted Factors In Embryogenesis For Protection ...mentioning

confidence: 99%

Section: Harnessing Secreted Factors In Embryogenesis For Protection ...mentioning

confidence: 99%

Charting the Path: Navigating Embryonic Development to Potentially Safeguard against Congenital Heart Defects

Bragança

Pinto

Silva

et al. 2023

JPM

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“…Many of these pathways are developmental pathways (10). The mutation may result in congenital heart abnormalities and alter the transcriptional processes of these genes (11).…”

Section: Introductionmentioning

confidence: 99%

Missense Mutations in the CITED2 Gene Contribute to Congenital Heart Disease

Yaqoob,

Ahmad

2024

Preprint

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Background Congenital heart disease (CHD) is a lifelong abnormality present from birth. Multiple studies have shown that mutations in genes involved in heart development could cause congenital heart disease. The CITED2 gene works as a transcription factor in the hypoxic pathway for the development of the heart. Therefore, five CHD types, ventricular septal defect, atrial septal defect, atrioventricular septal defect, tetralogy of Fallot, and patent ductus arteriosus, were evaluated by conducting a targeted single nucleotide polymorphism (SNP) analysis of the CITED2 gene variant rs375393125 (T > C). This study aimed to identify the association of CITED2 gene mutations in CHD patients. Methods A total of 350 samples were collected 250 from patients and 100 from controls for genetic analysis. Allele-specific PCR and gel electrophoresis were used to identify the target missense mutations. The genotypic results of the CHDs were further validated through Sanger sequencing. Results The frequency of the homozygous mutant (CC) in CHD patients was 48.4% and of heterozygous mutant (TC) genotype was 11.4%; these percentages are higher than controls (1%). The control samples had only one heterozygous TC and no homozygous CC genotype. The chi-square value was obtained at 103.9 with a probability of 0.05, which is greater than the significance value of 21.03. The odds ratio was 43.7, which is > 1. The calculated value of ANOVA was 11.6, which was more significant than the F critical value of 3.7. As a result of sequencing, the mutant sample of each selected CHD type was found heterozygous or homozygous and the results were like as those obtained through conventional PCR. Conclusion CHD patient’s samples showed mutations. Therefore, it can say that CITED2 gene SNP might be associated with CHD.

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CITED2 and the modulation of the hypoxic response in cancer

Fernandes¹,

Mendes-Silva²,

Bragança³

2020

WJCO

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CITED2 (CBP/p300-interacting transactivator with Glu/Asp-rich C-terminal domain, 2) is a ubiquitously expressed protein exhibiting a high affinity for the CH1 domain of the transcriptional co-activators CBP/p300, for which it competes with hypoxia-inducible factors (HIFs). CITED2 is particularly efficient in the inhibition of HIF-1α-dependent transcription in different contexts, ranging from organ development and metabolic homeostasis to tissue regeneration and immunity, being also potentially involved in various other physiological processes. In addition, CITED2 plays an important role in inhibiting HIF in some diseases, including kidney and heart diseases and type 2-diabetes. In the particular case of cancer, CITED2 either functions by promoting or suppressing cancer development depending on the context and type of tumors. For instance, CITED2 overexpression promotes breast and prostate cancers, as well as acute myeloid leukemia, while its expression is downregulated to sustain colorectal cancer and hepatocellular carcinoma. In addition, the role of CITED2 in the maintenance of cancer stem cells reveals its potential as a target in non-small cell lung carcinoma and acute myeloid leukemia, for example. But besides the wide body of evidence linking both CITED2 and HIF signaling to carcinogenesis, little data is available regarding CITED2 role as a negative regulator of HIF-1α specifically in cancer. Therefore, comprehensive studies exploring further the interactions of these two important mediators in cancer-specific models are sorely needed and this can potentially lead to the development of novel targeted therapies.

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CITED Proteins in the Heart of Pluripotent Cells and in Heart’s Full Potential

Cited by 3 publications

References 160 publications

Charting the Path: Navigating Embryonic Development to Potentially Safeguard against Congenital Heart Defects

Charting the Path: Navigating Embryonic Development to Potentially Safeguard against Congenital Heart Defects

Missense Mutations in the CITED2 Gene Contribute to Congenital Heart Disease

CITED2 and the modulation of the hypoxic response in cancer

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