Retinoic acid production by endocardium and epicardium is an injury response essential for zebrafish heart regeneration.
Retinoic acid production by endocardium and epicardium is an injury response essential for zebrafish heart regeneration.
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DOI：
10.1016/j.devcel.2011.01.010
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发表时间：
2011-03-15
影响因子：
11.8
通讯作者：
Poss, Kenneth D.
中科院分区：
文献类型：
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作者：
Kikuchi, Kazu;Holdway, Jennifer E.;Major, Robert J.;Blum, Nicola;Dahn, Randall D.;Begemann, Gerrit;Poss, Kenneth D.
斑马鱼的心脏再生是通过激活创伤区域的心肌细胞增殖来实现的。在这里，我们表明，在三个小时的心室损伤，整个心内膜经历了形态变化，并诱导了维甲酸(RA)合成酶raldh2的表达。到创伤后一天，raldh2的表达定位于损伤部位的心内膜细胞，随着心脏形成的开始，该区域补充了raldh2表达的心外膜细胞。诱导的RA受体转基因抑制或RA降解酶的表达阻止了再生心肌细胞的增殖。受损伤的远古鱼类Pypterus senegalus的心脏也诱导并保持了与心肌细胞增殖一致的心内膜和心外膜raldh2的强劲表达，而再生能力较差的梗塞小鼠心脏则没有。我们的发现表明，斑马鱼的心内膜是RA的动态、损伤反应来源，并表明心内膜和心外膜细胞在靶向受损心脏组织合成RA和促进心肌细胞增殖方面发挥关键作用。
Zebrafish heart regeneration occurs through the activation of cardiomyocyte proliferation in areas of trauma. Here, we show that within three hours of ventricular injury, the entire endocardium undergoes morphological changes and induces expression of the retinoic acid (RA)-synthesizing enzyme raldh2. By one day post-trauma, raldh2 expression becomes localized to endocardial cells at the injury site, an area that is supplemented with raldh2-expressing epicardial cells as cardiogenesis begins. Induced transgenic inhibition of RA receptors or expression of an RA-degrading enzyme blocked regenerative cardiomyocyte proliferation. Injured hearts of the ancient fish Polypterus senegalus also induced and maintained robust endocardial and epicardial raldh2 expression coincident with cardiomyocyte proliferation, while poorly regenerative infarcted murine hearts did not. Our findings reveal that the endocardium is a dynamic, injury-responsive source of RA in zebrafish, and indicate key roles for endocardial and epicardial cells in targeting RA synthesis to damaged heart tissue and promoting cardiomyocyte proliferation.
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影响因子：
9.8
作者：
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通讯作者：
Dvorak, Harold F.
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