Activation of Smad2 but not Smad3 is required to mediate TGF-β signaling during axolotl limb regeneration

被引:29
作者
Denis, Jean-Francois [1 ]
Sader, Fadi [1 ]
Gatien, Samuel [1 ]
Villiard, Eric [2 ]
Philip, Anie [3 ]
Roy, Stephane [1 ,2 ]
机构
[1] Univ Montreal, Fac Med, Dept Biochem & Mol Med, Montreal, PQ H3C 3J7, Canada
[2] Univ Montreal, Fac Dent, Dept Stomatol, Montreal, PQ H3C 3J7, Canada
[3] McGill Univ, Fac Med, Dept Surg, Montreal, PQ H3G 1A4, Canada
来源
DEVELOPMENT | 2016年 / 143卷 / 19期
基金
加拿大健康研究院;
关键词
Axolotl; Epimorphic; Regeneration; TGF-beta signaling; Smad2; Smad3; Limb; Salamander; Urodeles; Ambystoma mexicanum; COLLAGENASE-3; MMP-13; EXPRESSION; MATRIX-METALLOPROTEINASE; BASEMENT-MEMBRANE; GENE-EXPRESSION; TRANSFORMING GROWTH-FACTOR-BETA-1; POLARIZATION MICROSCOPY; TARGETED DISRUPTION; DIFFERENTIAL ROLES; TAIL REGENERATION; TISSUE INHIBITOR;
D O I
10.1242/dev.131466
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Axolotls are unique among vertebrates in their ability to regenerate tissues, such as limbs, tail and skin. The axolotl limb is the most studied regenerating structure. The process is well characterized morphologically; however, it is not well understood at the molecular level. We demonstrate that TGF-beta 1 is highly upregulated during regeneration and that TGF-beta signaling is necessary for the regenerative process. We show that the basement membrane is not prematurely formed in animals treated with the TGF-beta antagonist SB-431542. More importantly, Smad2 and Smad3 are differentially regulated post-translationally during the preparation phase of limb regeneration. Using specific antagonists for Smad2 and Smad3 we demonstrate that Smad2 is responsible for the action of TGF-beta during regeneration, whereas Smad3 is not required. Smad2 target genes (Mmp2 and Mmp9) are inhibited in SB-431542-treated limbs, whereas non-canonical TGF-beta targets (e.g. Mmp13) are unaffected. This is the first study to show that Smad2 and Smad3 are differentially regulated during regeneration and places Smad2 at the heart of TGF-beta signaling supporting the regenerative process.
引用
收藏
页码:3481 / 3490
页数:10
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