Myocardial β-Catenin-BMP2 signaling promotes mesenchymal cell proliferation during endocardial cushion formation.

Autor: Wang Y; Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, China; Department of Genetics, Albert Einstein College of Medicine, Bronx, New York, United States. Electronic address: yidwang119@mail.xjtu.edu.cn., Lu P; Department of Genetics, Albert Einstein College of Medicine, Bronx, New York, United States., Wu B; Department of Genetics, Albert Einstein College of Medicine, Bronx, New York, United States., Riascos-Bernal DF; Department of Medicine (Cardiology Division), Department of Developmental and Molecular Biology, Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, New York, United States., Sibinga NES; Department of Medicine (Cardiology Division), Department of Developmental and Molecular Biology, Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, New York, United States., Valenta T; Institute of Molecular Life Sciences, University of Zurich, Zurich, 8057, Switzerland., Basler K; Institute of Molecular Life Sciences, University of Zurich, Zurich, 8057, Switzerland., Zhou B; Department of Genetics, Albert Einstein College of Medicine, Bronx, New York, United States; Department of Genetics, Pediatrics, and Medicine (Cardiology), Wilf Family Cardiovascular Research Institute, Institute for Aging Research, Albert Einstein College of Medicine, Bronx, New York 10461, United States; Department of Cardiology, First Affiliated Hospital and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China. Electronic address: bin.zhou@einstein.yu.edu.
Jazyk: angličtina
Zdroj: Journal of molecular and cellular cardiology [J Mol Cell Cardiol] 2018 Oct; Vol. 123, pp. 150-158. Date of Electronic Publication: 2018 Sep 08.
DOI: 10.1016/j.yjmcc.2018.09.001
Abstrakt: Abnormal endocardial cushion formation is a major cause of congenital heart valve disease, which is a common birth defect with significant morbidity and mortality. Although β-catenin and BMP2 are two well-known regulators of endocardial cushion formation, their interaction in this process is largely unknown. Here, we report that deletion of β-catenin in myocardium results in formation of hypoplastic endocardial cushions accompanying a decrease of mesenchymal cell proliferation. Loss of β-catenin reduced Bmp2 expression in myocardium and SMAD signaling in cushion mesenchyme. Exogenous BMP2 recombinant proteins fully rescued the proliferation defect of mesenchymal cells in cultured heart explants from myocardial β-catenin knockout embryos. Using a canonical WNT signaling reporter mouse line, we showed that cushion myocardium exhibited high WNT/β-catenin activities during endocardial cushion growth. Selective disruption of the signaling function of β-catenin resulted in a cushion growth defect similar to that caused by the complete loss of β-catenin. Together, these observations demonstrate that myocardial β-catenin signaling function promotes mesenchymal cell proliferation and endocardial cushion expansion through inducing BMP signaling.
(Copyright © 2018. Published by Elsevier Ltd.)
Databáze: MEDLINE
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