Differential Regulation of Transforming Growth Factor β Signaling Pathways by Notch in Human Endothelial Cells

被引:89
作者
Fu, YangXin [2 ]
Chang, Alex
Chang, Linda
Niessen, Kyle
Eapen, Shawn
Setiadi, Audi
Karsan, Aly [1 ,2 ]
机构
[1] Univ British Columbia, British Columbia Canc Agcy, British Columbia Canc Res Ctr, Vancouver, BC V5Z 1L3, Canada
[2] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V5Z 1L3, Canada
基金
加拿大健康研究院;
关键词
CONGENITAL HEART-DEFECTS; TGF-BETA; MESENCHYMAL TRANSITION; CARDIAC DEVELOPMENT; TRANSCRIPTIONAL ACTIVATION; INTRACELLULAR DOMAIN; VASCULAR DEVELOPMENT; GENE-EXPRESSION; TARGET GENES; SMAD3;
D O I
10.1074/jbc.M109.011833
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Notch and transforming growth factor beta (TGF beta) play critical roles in endothelial-to-mesenchymal transition (EndMT), a process that is essential for heart development. Previously, we have shown that Notch and TGF beta signaling synergistically induce Snail expression in endothelial cells, which is required for EndMT in cardiac cushion morphogenesis. Here, we report that Notch activation modulates TGF beta signaling pathways in a receptor-activated Smad (R-Smad)-specific manner. Notch activation inhibits TGF beta/Smad1 and TGF beta/Smad2 signaling pathways by decreasing the expression of Smad1 and Smad2 and their target genes. In contrast, Notch increases SMAD3 mRNA expression and protein half-life and regulates the expression of TGF beta/Smad3 target genes in a gene-specific manner. Inhibition of Notch in the cardiac cushion of mouse embryonic hearts reduces Smad3 expression. Notch and TGF beta synergistically upregulate a subset of genes by recruiting Smad3 to both Smad and CSL binding sites and cooperatively inducing histone H4 acetylation. This is the first evidence that Notch activation affects R-Smad expression and that cooperative induction of histone acetylation at specific promoters underlies the selective synergy between Notch and TGF beta signaling pathways.
引用
收藏
页码:19452 / 19462
页数:11
相关论文
共 48 条
[1]   VE-cadherin-Cre-recombinase transgenic mouse: A tool for lineage analysis and gene deletion in endothelial cells [J].
Alva, JA ;
Zovein, AC ;
Monvoisin, A ;
Murphy, T ;
Salazar, A ;
Harvey, NL ;
Carmeliet, P ;
Iruela-Arispe, ML .
DEVELOPMENTAL DYNAMICS, 2006, 235 (03) :759-767
[2]   Heart valve development - Endothelial cell signaling and differentiation [J].
Armstrong, EJ ;
Bischoff, J .
CIRCULATION RESEARCH, 2004, 95 (05) :459-470
[3]   Notch signaling: Cell fate control and signal integration in development [J].
Artavanis-Tsakonas, S ;
Rand, MD ;
Lake, RJ .
SCIENCE, 1999, 284 (5415) :770-776
[4]   Smads as transcriptional co-modulators [J].
Attisano, L ;
Wrana, JL .
CURRENT OPINION IN CELL BIOLOGY, 2000, 12 (02) :235-243
[5]   Interaction and functional interplay between endoglin and ALK-1, two components of the endothelial transforming growth factor-β receptor complex [J].
Blanco, FJ ;
Santibanez, JF ;
Guerrero-Esteo, M ;
Langa, C ;
Vary, CPH ;
Bernabeu, C .
JOURNAL OF CELLULAR PHYSIOLOGY, 2005, 204 (02) :574-584
[6]   Cross-talk between the Notch and TGF-β signaling pathways mediated by interaction of the Notch intracellular domain with Smad3 [J].
Blokzijl, A ;
Dahlqvist, C ;
Reissmann, E ;
Falk, A ;
Moliner, A ;
Lendahl, U ;
Ibáñez, CF .
JOURNAL OF CELL BIOLOGY, 2003, 163 (04) :723-728
[7]   Notch pathway: Making sense of suppressor of hairless [J].
Bray, S ;
Furriols, M .
CURRENT BIOLOGY, 2001, 11 (06) :R217-R221
[8]   A tale of two proteins:: Differential roles and regulation of Smad2 and Smad3 in TGF-β signaling [J].
Brown, Kimberly A. ;
Pietenpol, Jennifer A. ;
Moses, Harold L. .
JOURNAL OF CELLULAR BIOCHEMISTRY, 2007, 101 (01) :9-33
[9]   The early-immediate gene EGR-1 is induced by transforming growth factor-β and mediates stimulation of collagen gene expression [J].
Chen, Shu-Jen ;
Ning, Hongyan ;
Ishida, Wataru ;
Sodin-Semrl, Snezna ;
Takagawa, Shinsuke ;
Mori, Yasuji ;
Varga, John .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (30) :21183-21197
[10]   Transcriptional deregulation and a missense mutation define ANKRD1 as a candidate gene for total anomalous pulmonary venous return [J].
Cinquetti, Raffaella ;
Badi, Ileana ;
Campione, Marina ;
Bortoletto, Elisabetta ;
Chiesa, Giulia ;
Parolini, Cinzia ;
Camesasca, Chiara ;
Russo, Antonella ;
Taramelli, Roberto ;
Acquatil, Francesco .
HUMAN MUTATION, 2008, 29 (04) :468-474