CXXC5 is required for cardiac looping relating to TGFβ signaling pathway in zebrafish

Peng, Xiyang; Li, Guanming; Wang, Yuequn; Zhuang, Jian; Luo, Rong; Chen, Jimei; Chen, Fa; Shi, Yan; Li, Jiani; Zhou, Zuoqiong; Mo, Xiaoyang; Xianchu, Liu; Yuan, Wuzhou; Zeng, Qun; Li, Yongqing; Jiang, Zhigang; Wan, Yongqi; Ye, Xiangli; Xu, Wei; Wang, Xijun; Fan, Xiongwei; Zhu, Ping; Wu, Xiushan; Deng, Yuan

doi:10.1016/j.ijcard.2016.03.201

Cited by 22 publications

(19 citation statements)

References 51 publications

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“…6% methylcellulose was used to restrict the movement of zebrafish and Axiocam of Zeiss Company was used to photograph and analyse the morphology of juvenile fish at 48 hpf and 72 hpf. The heart phenotype of the juvenile fish at these two stages were analysed as previously described 48 . The range of motion of the heart was clearly seen, and the approximate position of VOT was observed.…”

Section: Plasmid Construction the Construction Of Overexpression Plamentioning

confidence: 99%

BVES downregulation in non-syndromic tetralogy of fallot is associated with ventricular outflow tract stenosis

Shi

Wang

et al. 2020

Sci Rep

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BVES is a transmembrane protein, our previous work demonstrated that single nucleotide mutations of BVES in tetralogy of fallot (TOF) patients cause a downregulation of BVES transcription. However, the relationship between BVES and the pathogenesis of TOF has not been determined. Here we reported our research results about the relationship between BVES and the right ventricular outflow tract (RVOT) stenosis. BVES expression was significantly downregulated in most TOF samples compared with controls. The expression of the second heart field (SHF) regulatory network genes, including NKX2.5, GATA4 and HAND2, was also decreased in the TOF samples. In zebrafish, bves knockdown resulted in looping defects and ventricular outflow tract (VOT) stenosis, which was mostly rescued by injecting bves mRNA. bves knockdown in zebrafish also decreased the expression of SHF genes, such as nkx2.5, gata4 and hand2, consistent with the TOF samples` results. The dualfluorescence reporter system analysis showed that BVES positively regulated the transcriptional activity of GATA4, NKX2.5 and HAND2 promoters. In zebrafish, nkx2.5 mRNA partially rescued VOT stenosis caused by bves knockdown. These results indicate that BVES downregulation may be associated with RVOT stenosis of non-syndromic TOF, and bves is probably involved in the development of VOT in zebrafish. Congenital heart disease (CHD) is the most common birth defect, exhibiting a mortality rate of more than 29% 1. Within this group of conditions, the incidence of TOF is 7-10% in the USA 2 , 13.4% in Nigeria 3 , and 16% in India 4. However, the aetiology of TOF has not been fully elucidated. Anatomically, TOF has four distinct structural defects, namely, ventricular septal defect, overriding of the aorta, RVOT/pulmonary artery (PA) stenosis and right ventricular hypertrophy 5. However, embryologically, the defects are thought to be caused by a single developmental error, involving the outflow tract funnel septum shifting left to right or forward, leading to a poor contraposition ventricular septal defect, overriding of the aorta and RVOT funnel stenosis 5-11. RVOT stenosis eventually leads to right ventricular hypertrophy 10. The degree of RVOT stenosis is a key clinical factor for the diagnosis of TOF 10. However, the molecular mechanism behind RVOT/PA stenosis remains under investigation. The development of the cardiac outflow tract has two major cell sources: one is neural crest cells, which provide cells for the distal development of the great artery by migration, while releasing signals to the SHF 7 ; the other

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Section: Plasmid Construction the Construction Of Overexpression Plamentioning

confidence: 99%

BVES downregulation in non-syndromic tetralogy of fallot is associated with ventricular outflow tract stenosis

Shi

Wang

et al. 2020

Sci Rep

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“…Fractional shortening of the ventricles and heart rate was calculated using software from the Noldus company (https://www.noldus.com/). Measurement for cardiac looping angle at 48hpf was done as Xiyang Peng et al (2016) [40] and Priya Choudhry et al (2013) [41] described.…”

Section: Zebrafish Embryo Manipulation In Situ Hybridization In Vitmentioning

confidence: 99%

CFTR deficiency causes cardiac dysplasia during zebrafish embryogenesis and is associated with dilated cardiomyopathy

Liu

Lin

Liao

et al. 2020

Mechanisms of Development

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Background: Mutations in the CFTR gene cause cystic fibrosis (CF) with myocardial dysfunction. However, it remains unknown whether CF-related heart disease is a secondary effect of pulmonary disease, or an intrinsic primary defect in the CF heart. Results: Here, we used a zebrafish model, which lacks lung tissue, to investigate the role of CFTR in cardiogenesis during embryonic development. Our findings demonstrate that a loss of CFTR impairs cardiac development from the cardiac progenitor stage of heart development, resulting in cardiac looping defects, a dilated atrium, pericardial edema, and a decrease in heart rate. Furthermore, we found that cardiac development is perturbed in wild type embryos treated with a gating specific Cftr channel inhibitor, CFTRinh-172, at the blastula stage of development, but not with treatment at later stages. Gene expression analysis of blastulas indicated that transcript levels, including mRNAs associated with cardiovascular diseases, were significantly altered in embryos derived from cftr mutants relative to controls. To evaluate the role of CFTR in human heart failure, we performed a genetic association study on individuals with dilated cardiomyopathy and found that CFTR containing I556V mutation, which causes a channel defect, is associated with the disease. Similar to well-studied channel-defective CFTR mutants, CFTR I556V mRNA failed to restore cardiac dysplasia in mutant embryos. Conclusions: The present study reveals an important role for the CFTR ion channel in regulating cardiac development during early embryogenesis, supporting the hypothesis that CF-related heart disease results from an intrinsic primary defect in the CF heart.

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“…Moreover, the CXXC5 protein associates with the histone deacetylase HDAC1 in HCC cells and competes for Smad2/3 binding, therefore alleviating HDAC1‐mediated signaling inhibition. Intriguingly, CXXC5 was also suggested to interact with Smad2/3 and Smad4 to promote TNF‐α‐induced apoptosis of primary cortical neurons and normal heart development and function in zebrafish …”

Section: Cxxc5 Functions As a Signaling Regulator And Mediatormentioning

confidence: 99%

“…was also suggested to interact with Smad2/3 and Smad4 to promote TNF-α-induced apoptosis of primary cortical neurons and normal heart development and function in zebrafish. 49,50…”

Section: Cxxc5 In Tgf-β/bmp Signalingmentioning

confidence: 99%

CXXC5: A novel regulator and coordinator of TGF‐β, BMP and Wnt signaling

Xiong

Wang

et al. 2018

J Cellular Molecular Medi

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CXXC5 is a member of the CXXC‐type zinc‐finger protein family. Proteins in this family play a pivotal role in epigenetic regulation by binding to unmethylated CpG islands in gene promoters through their characteristic CXXC domain. CXXC5 is a short protein (322 amino acids in length) that does not have any catalytic domain, but is able to bind to DNA and act as a transcription factor and epigenetic factor through protein‐protein interactions. Intriguingly, increasing evidence indicates that expression of the CXXC5 gene is controlled by multiple signaling pathways and a variety of transcription factors, positioning CXXC5 as an important signal integrator. In addition, CXXC5 is capable of regulating various signal transduction processes, including the TGF‐β, Wnt and ATM‐p53 pathways, thereby acting as a novel and crucial signaling coordinator. CXXC5 plays an important role in embryonic development and adult tissue homeostasis by regulating cell proliferation, differentiation and apoptosis. In keeping with these functions, aberrant expression or altered activity of CXXC5 has been shown to be involved in several human diseases including tumourigenesis. This review summarizes the current understanding of CXXC5 as a transcription factor and signaling regulator and coordinator.

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CXXC5 is required for cardiac looping relating to TGFβ signaling pathway in zebrafish

Cited by 22 publications

References 51 publications

BVES downregulation in non-syndromic tetralogy of fallot is associated with ventricular outflow tract stenosis

BVES downregulation in non-syndromic tetralogy of fallot is associated with ventricular outflow tract stenosis

CFTR deficiency causes cardiac dysplasia during zebrafish embryogenesis and is associated with dilated cardiomyopathy

CXXC5: A novel regulator and coordinator of TGF‐β, BMP and Wnt signaling

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