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Updated: Dec 20, 2025

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling
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Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling

Published on: August 3, 2018

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Transforming Growth Factor Beta3 is Required for Cardiovascular Development

Mrinmay Chakrabarti1, Nadia Al-Sammarraie1, Mengistu G Gebere1

  • 1Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC 29209, USA.

Journal of Cardiovascular Development and Disease
|May 28, 2020
PubMed

Insights

Transforming growth factor beta3 (TGFB3) is essential for proper cardiovascular development. Its absence in mice leads to diverse heart defects, highlighting its role in maintaining TGFβ signaling balance.

Area of Science:

  • Cardiovascular Biology
  • Developmental Biology
  • Genetics

Background:

  • Mutations in Transforming growth factor beta3 (TGFB3) are linked to conditions like arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD1) and Loeys-Dietz syndrome-5 (LDS5).
  • The precise role of TGFB3 in embryonic cardiovascular development and disease remains largely undefined.

Purpose of the Study:

  • To investigate the function of TGFB3 in cardiovascular development and disease using a mouse model.
  • To elucidate the molecular mechanisms underlying TGFB3's role in cardiac formation.

Main Methods:

  • Histological, immunohistochemical, and molecular analyses were performed on TGFB3-deficient (Tgfb3-/-) fetal hearts.
  • In vitro studies utilized TGFB3-deficient fibroblasts in 3-D collagen lattice assays.
  • Biochemical analyses assessed canonical (SMAD-dependent) and noncanonical (MAP kinase-dependent) TGFβ signaling pathways.

Main Results:

  • Approximately two-thirds of Tgfb3-/- fetuses exhibited cardiovascular malformations, including ventricular myocardium abnormalities, outflow tract defects, and valve thickening.
  • Ventricular septal defects (VSDs) were observed in Tgfb3-/- fetuses, often associated with myocardial defects.
  • TGFB3 deficiency impaired collagen matrix reorganization in vitro and led to paradoxical activation of canonical and noncanonical TGFβ signaling pathways.

Conclusions:

  • TGFB3 is crucial for normal cardiovascular development, preventing a range of congenital heart defects.
  • The study demonstrates TGFB3's requirement for maintaining a balance between canonical and noncanonical TGFβ signaling pathways during heart development.

Keywords:
arrhythmogenic right ventricular dysplasiacardiac developmentcleft palatecongenital heart diseaseloeys dietz syndrome-5outflow tract septationrienhoff syndromesignaling networkstransforming growth factor beta-3

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