Article: Smad7 is required for the development and function of the heart
| Title | Smad7 is required for the development and function of the heart | ||||||||||||||
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| Authors | Chen, 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 Chen, Y3 | ||||||||||||||
| Keywords | Species Index: Mus | ||||||||||||||
| Issue Date | 2009 | ||||||||||||||
| Publisher | American 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?] DOI: http://dx.doi.org/10.1074/jbc.M807233200 | ||||||||||||||
| 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. © 2009 by The American Society for Biochemistry and Molecular Biology, Inc. | ||||||||||||||
| ISSN | 0021-9258 2011 Impact Factor: 4.773 2011 SCImago Journal Rankings: 0.793 | ||||||||||||||
| DOI | http://dx.doi.org/10.1074/jbc.M807233200 | ||||||||||||||
| ISI Accession Number ID | WOS:000261974800033
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.). | ||||||||||||||
| PubMed Central ID | PMC2610499 | ||||||||||||||
| References | References in Scopus |
| dc.contributor.author | Chen, Q | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| dc.contributor.author | Chen, H | ||||||||||||||
| dc.contributor.author | Zheng, D | ||||||||||||||
| dc.contributor.author | Kuang, C | ||||||||||||||
| dc.contributor.author | Fang, H | ||||||||||||||
| dc.contributor.author | Zou, B | ||||||||||||||
| dc.contributor.author | Zhu, W | ||||||||||||||
| dc.contributor.author | Bu, G | ||||||||||||||
| dc.contributor.author | Jin, T | ||||||||||||||
| dc.contributor.author | Wang, Z | ||||||||||||||
| dc.contributor.author | Zhang, X | ||||||||||||||
| dc.contributor.author | Chen, J | ||||||||||||||
| dc.contributor.author | Field, LJ | ||||||||||||||
| dc.contributor.author | Rubart, M | ||||||||||||||
| dc.contributor.author | Shou, W | ||||||||||||||
| dc.contributor.author | Chen, Y | ||||||||||||||
| dc.date.accessioned | 2010-09-17T10:43:04Z | ||||||||||||||
| dc.date.available | 2010-09-17T10:43:04Z | ||||||||||||||
| dc.date.issued | 2009 | ||||||||||||||
| dc.description.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. © 2009 by The American Society for Biochemistry and Molecular Biology, Inc. | ||||||||||||||
| dc.description.nature | Link_to_subscribed_fulltext | ||||||||||||||
| dc.identifier.citation | Journal 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.doi | http://dx.doi.org/10.1074/jbc.M807233200 | ||||||||||||||
| dc.identifier.eissn | 1083-351X | ||||||||||||||
| dc.identifier.epage | 300 | ||||||||||||||
| dc.identifier.isi | WOS:000261974800033
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.issn | 0021-9258 2011 Impact Factor: 4.773 2011 SCImago Journal Rankings: 0.793 | ||||||||||||||
| dc.identifier.issue | 1 | ||||||||||||||
| dc.identifier.pmcid | PMC2610499 | ||||||||||||||
| dc.identifier.pmid | 18952608 | ||||||||||||||
| dc.identifier.scopus | eid_2-s2.0-58649111523 | ||||||||||||||
| dc.identifier.spage | 292 | ||||||||||||||
| dc.identifier.uri | http://hdl.handle.net/10722/92337 | ||||||||||||||
| dc.identifier.volume | 284 | ||||||||||||||
| dc.language | eng | ||||||||||||||
| dc.publisher | American Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/ | ||||||||||||||
| dc.relation.ispartof | Journal of Biological Chemistry | ||||||||||||||
| dc.relation.references | References in Scopus | ||||||||||||||
| dc.subject | Species Index: Mus | ||||||||||||||
| dc.title | Smad7 is required for the development and function of the heart | ||||||||||||||
| dc.type | Article |
Author Affiliations
- Indiana University School of Medicine Indianapolis
- University of California, San Diego
- Shanghai Institute for Biological Sciences Chinese Academy of Sciences