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Article: Smad7 is required for the development and function of the heart

TitleSmad7 is required for the development and function of the heart
Authors
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/
Citation
Journal of Biological Chemistry, 2009, v. 284 n. 1, p. 292-300 How to Cite?
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.
Persistent Identifierhttp://hdl.handle.net/10722/92337
ISSN
2014 Impact Factor: 4.573
2014 SCImago Journal Rankings: 2.734
PubMed Central ID
ISI Accession Number ID
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.).

References

 

DC FieldValueLanguage
dc.contributor.authorChen, Qen_HK
dc.contributor.authorChen, Hen_HK
dc.contributor.authorZheng, Den_HK
dc.contributor.authorKuang, Cen_HK
dc.contributor.authorFang, Hen_HK
dc.contributor.authorZou, Ben_HK
dc.contributor.authorZhu, Wen_HK
dc.contributor.authorBu, Gen_HK
dc.contributor.authorJin, Ten_HK
dc.contributor.authorWang, Zen_HK
dc.contributor.authorZhang, Xen_HK
dc.contributor.authorChen, Jen_HK
dc.contributor.authorField, LJen_HK
dc.contributor.authorRubart, Men_HK
dc.contributor.authorShou, Wen_HK
dc.contributor.authorChen, Yen_HK
dc.date.accessioned2010-09-17T10:43:04Z-
dc.date.available2010-09-17T10:43:04Z-
dc.date.issued2009en_HK
dc.identifier.citationJournal of Biological Chemistry, 2009, v. 284 n. 1, p. 292-300en_HK
dc.identifier.issn0021-9258en_HK
dc.identifier.urihttp://hdl.handle.net/10722/92337-
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.en_HK
dc.languageengen_HK
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/en_HK
dc.relation.ispartofJournal of Biological Chemistryen_HK
dc.subjectSpecies Index: Musen_HK
dc.titleSmad7 is required for the development and function of the hearten_HK
dc.typeArticleen_HK
dc.identifier.emailChen, Y:ychenc@hkucc.hku.hken_HK
dc.identifier.authorityChen, Y=rp1318en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1074/jbc.M807233200en_HK
dc.identifier.pmid18952608-
dc.identifier.pmcidPMC2610499-
dc.identifier.scopuseid_2-s2.0-58649111523en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-58649111523&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume284en_HK
dc.identifier.issue1en_HK
dc.identifier.spage292en_HK
dc.identifier.epage300en_HK
dc.identifier.eissn1083-351X-
dc.identifier.isiWOS:000261974800033-

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