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Article: Smad7 is required for the development and function of the heart
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TitleSmad7 is required for the development and function of the heart
 
AuthorsChen, Q1
Chen, H1
Zheng, D3
Kuang, C
Fang, H1
Zou, B
Zhu, W1
Bu, G1
Jin, T3
Wang, Z3
Zhang, X
Chen, J2
Field, LJ1
Rubart, M1
Shou, W1 1
Chen, Y3
 
KeywordsSpecies Index: Mus
 
Issue Date2009
 
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
 
CitationJournal of Biological Chemistry, 2009, v. 284 n. 1, p. 292-300 [How to Cite?]
DOI: http://dx.doi.org/10.1074/jbc.M807233200
 
AbstractTransforming 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. © 2009 by The American Society for Biochemistry and Molecular Biology, Inc.
 
ISSN0021-9258
2012 Impact Factor: 4.651
2012 SCImago Journal Rankings: 2.723
 
DOIhttp://dx.doi.org/10.1074/jbc.M807233200
 
PubMed Central IDPMC2610499
 
ISI Accession Number IDWOS:000261974800033
Funding AgencyGrant Number
National Institutes of HealthR21-CA122764
03-HD049556
R01-HL81092
R01-HL70259
P01-HL85098
Indiana Genomics Initiative (INGEN)
National Natural Science Foundation of China30588002
Ministry of Science and Technology of China2006CB943902
2007CB947100
Science & Technology Commission of Shanghai Municipality07DJ14005
Riley Children Foundation
Funding Information:

This work was supported, in whole or in part, by National Institutes of Health Grants R21-CA122764 and R03-HD049556, by NIH Grants R01-HL81092 and R01-HL70259 (to W. S.), and by NIH Grant P01-HL85098 (to L.J.F. and W.S.). This work was also supported by the Indiana Genomics Initiative (INGEN), the National Natural Science Foundation of China (Grant 30588002), the Ministry of Science and Technology of China (Grants 2006CB943902 and 2007CB947100), the Science & Technology Commission of Shanghai Municipality (Grant 07DJ14005) (to Y.C.), and the Riley Children Foundation (to W. S. and L.J.F.).

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorChen, Q
 
dc.contributor.authorChen, H
 
dc.contributor.authorZheng, D
 
dc.contributor.authorKuang, C
 
dc.contributor.authorFang, H
 
dc.contributor.authorZou, B
 
dc.contributor.authorZhu, W
 
dc.contributor.authorBu, G
 
dc.contributor.authorJin, T
 
dc.contributor.authorWang, Z
 
dc.contributor.authorZhang, X
 
dc.contributor.authorChen, J
 
dc.contributor.authorField, LJ
 
dc.contributor.authorRubart, M
 
dc.contributor.authorShou, W
 
dc.contributor.authorChen, Y
 
dc.date.accessioned2010-09-17T10:43:04Z
 
dc.date.available2010-09-17T10:43:04Z
 
dc.date.issued2009
 
dc.description.abstractTransforming 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. © 2009 by The American Society for Biochemistry and Molecular Biology, Inc.
 
dc.description.natureLink_to_subscribed_fulltext
 
dc.identifier.citationJournal of Biological Chemistry, 2009, v. 284 n. 1, p. 292-300 [How to Cite?]
DOI: http://dx.doi.org/10.1074/jbc.M807233200
 
dc.identifier.doihttp://dx.doi.org/10.1074/jbc.M807233200
 
dc.identifier.eissn1083-351X
 
dc.identifier.epage300
 
dc.identifier.isiWOS:000261974800033
Funding AgencyGrant Number
National Institutes of HealthR21-CA122764
03-HD049556
R01-HL81092
R01-HL70259
P01-HL85098
Indiana Genomics Initiative (INGEN)
National Natural Science Foundation of China30588002
Ministry of Science and Technology of China2006CB943902
2007CB947100
Science & Technology Commission of Shanghai Municipality07DJ14005
Riley Children Foundation
Funding Information:

This work was supported, in whole or in part, by National Institutes of Health Grants R21-CA122764 and R03-HD049556, by NIH Grants R01-HL81092 and R01-HL70259 (to W. S.), and by NIH Grant P01-HL85098 (to L.J.F. and W.S.). This work was also supported by the Indiana Genomics Initiative (INGEN), the National Natural Science Foundation of China (Grant 30588002), the Ministry of Science and Technology of China (Grants 2006CB943902 and 2007CB947100), the Science & Technology Commission of Shanghai Municipality (Grant 07DJ14005) (to Y.C.), and the Riley Children Foundation (to W. S. and L.J.F.).

 
dc.identifier.issn0021-9258
2012 Impact Factor: 4.651
2012 SCImago Journal Rankings: 2.723
 
dc.identifier.issue1
 
dc.identifier.pmcidPMC2610499
 
dc.identifier.pmid18952608
 
dc.identifier.scopuseid_2-s2.0-58649111523
 
dc.identifier.spage292
 
dc.identifier.urihttp://hdl.handle.net/10722/92337
 
dc.identifier.volume284
 
dc.languageeng
 
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
 
dc.relation.ispartofJournal of Biological Chemistry
 
dc.relation.referencesReferences in Scopus
 
dc.subjectSpecies Index: Mus
 
dc.titleSmad7 is required for the development and function of the heart
 
dc.typeArticle
 
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Author Affiliations
  1. Indiana University School of Medicine Indianapolis
  2. University of California, San Diego
  3. Shanghai Institute for Biological Sciences Chinese Academy of Sciences