PUBLICATION

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

Authors
Shi, Y., Li, Y., Wang, Y., Zhu, P., Chen, Y., Wang, H., Yue, S., Xia, X., Chen, J., Jiang, Z., Zhou, C., Cai, W., Yuan, H., Wu, Y., Wan, Y., Li, X., Zhu, X., Zhou, Z., Dai, G., Li, F., Mo, X., Ye, X., Fan, X., Zhuang, J., Wu, X., Yuan, W.
ID
ZDB-PUB-200828-5
Date
2020
Source
Scientific Reports   10: 14167 (Journal)
Registered Authors
Keywords
none
MeSH Terms
  • Tetralogy of Fallot/complications
  • Tetralogy of Fallot/genetics*
  • Tetralogy of Fallot/metabolism
  • Tetralogy of Fallot/pathology
  • Ventricular Outflow Obstruction/embryology
  • Ventricular Outflow Obstruction/etiology
  • Ventricular Outflow Obstruction/genetics*
  • Heart/embryology
  • Coronary Vessel Anomalies
  • Middle Aged
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/physiology
  • Muscle Proteins/biosynthesis*
  • Muscle Proteins/genetics
  • Muscle Proteins/physiology
  • Female
  • Homeobox Protein Nkx-2.5/genetics
  • Homeobox Protein Nkx-2.5/physiology
  • Down-Regulation
  • Animals
  • Infant
  • Foramen Ovale, Patent
  • Male
  • Zebrafish/embryology
  • Abnormalities, Multiple
  • Child, Preschool
  • Child
  • Disease Models, Animal
  • Humans
  • Cell Adhesion Molecules/biosynthesis*
  • Cell Adhesion Molecules/genetics
  • Cell Adhesion Molecules/physiology
  • Gene Expression Regulation
  • RNA, Messenger/genetics
(all 34)
PubMed
32843646 Full text @ Sci. Rep.
Abstract
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 dual-fluorescence 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.
Genes / Markers
Figures
Figure Gallery (5 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
pd15TgTransgenic Insertion
    y1TgTransgenic Insertion
      1 - 2 of 2
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      Human Disease / Model
      Human Disease Fish Conditions Evidence
      tetralogy of FallotAB + MO1-popdc1standard conditionsTAS
      1 - 1 of 1
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      Sequence Targeting Reagents
      Target Reagent Reagent Type
      popdc1MO1-popdc1MRPHLNO
      1 - 1 of 1
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      Fish
      Antibodies
      No data available
      Orthology
      No data available
      Engineered Foreign Genes
      Marker Marker Type Name
      DsRed2EFGDsRed2
      EGFPEFGEGFP
      1 - 2 of 2
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      Mapping
      No data available