Smad7 is required for the development and function of the heart

Qian Chen, Hanying Chen, Dawei Zheng, Chenzhong Kuang, Hong Fang, Bingyu Zou, Wuqiang Zhu, Guixue Bu, Ting Jin, Zhenzhen Wang, Xin Zhang, Ju Chen, Loren Field, Michael Rubart-von der Lohe, Weinian Shou, Yan Chen

Research output: Contribution to journalArticle

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Abstract

Transforming growth factor-β (TGF-β) family members, including TGF-βs, activins, and bone morphogenetic proteins, exert diverse biological activities in cell proliferation, differentiation, apoptosis, embryonic development, and many other processes. These effects are largely mediated by Smad proteins. Smad7 is a negative regulator for the signaling of TGF-β family members. Dysregulation of Smad7 is associated with pathogenesis of a variety of human diseases. However, the in vivo physiological roles of Smad7 have not been elucidated due to the lack of a mouse model with significant loss of Smad7 function. Here we report generation and initial characterization of Smad7 mutant mice with targeted deletion of the indispensable MH2 domain. The majority of Smad7 mutant mice died in utero due to multiple defects in cardiovascular development, including ventricular septal defect and non-compaction, as well as outflow tract malformation. The surviving adult Smad7 mutant mice had impaired cardiac functions and severe arrhythmia. Further analyses suggest that Smad2/3 phosphorylation was elevated in atrioventricular cushion in the heart ofSmad7 mutant mice, accompanied by increased apoptosis in this region. Taken together, these observations pinpoint an important role of Smad7 in the development and function of the mouse heart in vivo.

Original languageEnglish
Pages (from-to)292-300
Number of pages9
JournalJournal of Biological Chemistry
Volume284
Issue number1
DOIs
StatePublished - Jan 2 2009

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Transforming Growth Factors
Smad Proteins
Apoptosis
Activins
Defects
Bone Morphogenetic Proteins
Phosphorylation
Cell proliferation
Bioactivity
Ventricular Heart Septal Defects
Embryonic Development
Cardiac Arrhythmias
Cell Differentiation
Cell Proliferation

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Smad7 is required for the development and function of the heart. / Chen, Qian; Chen, Hanying; Zheng, Dawei; Kuang, Chenzhong; Fang, Hong; Zou, Bingyu; Zhu, Wuqiang; Bu, Guixue; Jin, Ting; Wang, Zhenzhen; Zhang, Xin; Chen, Ju; Field, Loren; Rubart-von der Lohe, Michael; Shou, Weinian; Chen, Yan.

In: Journal of Biological Chemistry, Vol. 284, No. 1, 02.01.2009, p. 292-300.

Research output: Contribution to journalArticle

Chen, Q, Chen, H, Zheng, D, Kuang, C, Fang, H, Zou, B, Zhu, W, Bu, G, Jin, T, Wang, Z, Zhang, X, Chen, J, Field, L, Rubart-von der Lohe, M, Shou, W & Chen, Y 2009, 'Smad7 is required for the development and function of the heart', Journal of Biological Chemistry, vol. 284, no. 1, pp. 292-300. https://doi.org/10.1074/jbc.M807233200
Chen, Qian ; Chen, Hanying ; Zheng, Dawei ; Kuang, Chenzhong ; Fang, Hong ; Zou, Bingyu ; Zhu, Wuqiang ; Bu, Guixue ; Jin, Ting ; Wang, Zhenzhen ; Zhang, Xin ; Chen, Ju ; Field, Loren ; Rubart-von der Lohe, Michael ; Shou, Weinian ; Chen, Yan. / Smad7 is required for the development and function of the heart. In: Journal of Biological Chemistry. 2009 ; Vol. 284, No. 1. pp. 292-300.
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