Journal article
Myocardial TGF beta 2 Is Required for Atrioventricular Cushion Remodeling and Myocardial Development
Journal of cardiovascular development and disease, v 8(3), 26
01 Mar 2021
PMID: 33801433
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Among the three transforming growth factor beta (TGF beta) ligands, TGF beta 2 is essential for heart development and is produced by multiple cell types, including myocardium. Heterozygous mutations in TGFB2 in patients of connective tissue disorders result in congenital heart defects and adult valve malformations, including mitral valve prolapse (MVP) with or without regurgitation. Tgfb2 germline knockout fetuses exhibit multiple cardiac defects but the role of myocardial-TGF beta 2 in heart development is yet to be elucidated. Here, myocardial Tgfb2 conditional knockout (CKO) embryos were generated by crossing Tgfb2(flox) mice with Tgfb2(+/-); cTntCre mice. Tgfb2(flox/-) embryos were normal, viable. Cell fate mapping was done using dual-fluorescent mT/mG(+/-) mice. Cre-mediated Tgfb2 deletion was assessed by genomic PCR. RNAscope in situ hybridization was used to detect the loss of myocardial Tgfb2 expression. Histological, morphometric, immunohistochemical, and in situ hybridization analyses of CKOs and littermate controls at different stages of heart development (E12.5-E18.5) were used to determine the role of myocardium-derived TGF beta 2 in atrioventricular (AV) cushion remodeling and myocardial development. CKOs exhibit a thin ventricular myocardium, AV cushion remodeling defects and developed incomplete AV septation defects. The loss of myocardial Tgfb2 resulted in impaired cushion maturation and dysregulated cell death. Phosphorylated SMAD2, a surrogate for TGF beta signaling, was "paradoxically" increased in both AV cushion mesenchyme and ventricular myocardium in the CKOs. Our results indicate that TGF beta 2 produced by cardiomyocytes acting as cells autonomously on myocardium and via paracrine signaling on AV cushions are required for heart development.
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Details
- Title
- Myocardial TGF beta 2 Is Required for Atrioventricular Cushion Remodeling and Myocardial Development
- Creators
- Aniket Bhattacharya - University of South CarolinaNadia Al-Sammarraie - University of South CarolinaMengistu G. Gebere - University of South CarolinaJohn Johnson - University of South CarolinaJohn F. Eberth - University of South CarolinaMohamad Azhar - University of South Carolina
- Publication Details
- Journal of cardiovascular development and disease, v 8(3), 26
- Publisher
- Mdpi
- Number of pages
- 15
- Grant note
- R01HL126705; R01HL145064; R01HL145064-01S1 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA University of South Carolina, School of Medicine (Bob Price-Instrumentation Resource Facility Endowment Fund)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000633803600001
- Scopus ID
- 2-s2.0-85102737162
- Other Identifier
- 991021902497704721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Cardiac & Cardiovascular Systems