Transforming Growth Factor Beta2 Is Required for Valve Remodeling During Heart Development

被引:56
作者
Azhar, Mohamad [1 ,2 ]
Brown, Kristen [1 ]
Gard, Connie [1 ]
Chen, Hwudaurw [2 ]
Rajan, Sudarsan [3 ]
Elliott, David A. [2 ]
Stevens, Mark V. [4 ]
Camenisch, Todd D. [4 ,5 ,6 ]
Conway, Simon J. [7 ]
Doetschman, Thomas [1 ,2 ]
机构
[1] Univ Arizona, Inst BIO5, Tucson, AZ USA
[2] Univ Arizona, Dept Cellular & Mol Med, Tucson, AZ USA
[3] Univ Cincinnati, Coll Med, Dept Mol Genet, Cincinnati, OH USA
[4] Univ Arizona, Dept Pharmacol & Toxicol, Tucson, AZ 85721 USA
[5] Univ Arizona, Steele Childrens Res Ctr, Tucson, AZ 85721 USA
[6] Univ Arizona, SW Environm Hlth Sci Ctr, Tucson, AZ 85721 USA
[7] Indiana Univ Sch Med, Herman B Wells Ctr Pediat Res, Dev Biol & Neonatal Med Program, Indianapolis, IN USA
基金
美国国家卫生研究院;
关键词
transforming growth factor beta; valves; heart development; TGF-BETA; EXTRACELLULAR-MATRIX; ENDOCARDIAL CUSHION; CELL-TRANSFORMATION; HEMATOPOIETIC STEM; AORTIC-ANEURYSMS; OUTFLOW TRACT; MOUSE MODELS; DIFFERENTIATION; EXPRESSION;
D O I
10.1002/dvdy.22702
中图分类号
R602 [外科病理学、解剖学]; R32 [人体形态学];
学科分类号
100123 [人体微生态学]; 100210 [外科学];
摘要
Although the function of transforming growth factor beta2 (TGF beta 2) in epithelial mesenchymal transition (EMT) is well studied, its role in valve remodeling remains to be fully explored. Here, we used histological, morphometric, immunohistochemical and molecular approaches and showed that significant dysregulation of major extracellular matrix (ECM) components contributed to valve remodeling defects in Tgfb2(-/-) embryos. The data indicated that cushion mesenchymal cell differentiation was impaired in Tgfb2(-/-) embryos. Hyaluronan and cartilage link protein-1 (CRTL1) were increased in hyperplastic valves of Tgfb2(-/-) embryos, indicating increased expansion and diversification of cushion mesenchyme into the cartilage cell lineage during heart development. Finally, Western blot and immunohistochemistry analyses indicate that the activation of SMAD2/3 was decreased in Tgfb2(-/-) embryos during valve remodeling. Collectively, the data indicate that TGF beta 2 promotes valve remodeling and differentiation by inducing matrix organization and suppressing cushion mesenchyme differentiation into cartilage cell lineage during heart development. Developmental Dynamics 240:2127-2141, 2011. (C) 2011 Wiley-Liss, Inc.
引用
收藏
页码:2127 / 2141
页数:15
相关论文
共 80 条
[1]
Cell death and differentiation in the development of the endocardial cushion of the embryonic heart [J].
Abdelwahid, E ;
Pelliniemi, LJ ;
Jokinen, E .
MICROSCOPY RESEARCH AND TECHNIQUE, 2002, 58 (05) :395-403
[2]
Transforming growth factor-beta(1) stimulates multiple protein interactions at a unique cis-element in the 3'-untranslated region of the hyaluronan receptor RHAMM mRNA [J].
Amara, FM ;
Entwistle, J ;
Kuschak, TI ;
Turley, EA ;
Wright, JA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (25) :15279-15284
[3]
TGFβ Signaling and Congenital Heart Disease: Insights from Mouse Studies [J].
Arthur, Helen M. ;
Bamforth, Simon D. .
BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY, 2011, 91 (06) :423-434
[4]
A Quantitative Trait Locus on Chromosome 4 Affects Cycling of Hematopoietic Stem and Progenitor Cells through Regulation of TGF-β2 Responsiveness [J].
Avagyan, Serine ;
Glouchkova, Ludmila ;
Choi, Juhyun ;
Snoeck, Hans-Willem .
JOURNAL OF IMMUNOLOGY, 2008, 181 (09) :5904-5911
[5]
Transforming growth factor beta in cardiovascular development and function [J].
Azhar, M ;
Schultz, JEJ ;
Grupp, I ;
Dorn, GW ;
Meneton, P ;
Molin, DGM ;
Gittenberger-de Groot, AC ;
Doetschman, T .
CYTOKINE & GROWTH FACTOR REVIEWS, 2003, 14 (05) :391-407
[6]
Ligand-Specific Function of Transforming Growth Factor Beta in Epithelial-Mesenchymal Transition in Heart Development [J].
Azhar, Mohamad ;
Runyan, Raymond B. ;
Gard, Connie ;
Sanford, L. Philip ;
Miller, Marian L. ;
Andringa, Anastasia ;
Pawlowski, Sharon ;
Rajan, Sudarsan ;
Doetschman, Thomas .
DEVELOPMENTAL DYNAMICS, 2009, 238 (02) :431-442
[7]
Bartram U, 2001, CIRCULATION, V103, P2745
[8]
Bouman HGA, 1997, ANAT RECORD, V248, P242
[9]
BREWER RJ, 1977, J THORAC CARDIOV SUR, V74, P645
[10]
Requirement of type III TGF-β receptor for endocardial cell transformation in the heart [J].
Brown, CB ;
Boyer, AS ;
Runyan, RB ;
Barnett, JV .
SCIENCE, 1999, 283 (5410) :2080-2082