Igf Signaling is Required for Cardiomyocyte Proliferation during Zebrafish Heart Development and Regeneration.
Igf Signaling is Required for Cardiomyocyte Proliferation during Zebrafish Heart Development and Regeneration.
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DOI：
10.1371/journal.pone.0067266
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Lien CL
中科院分区：
文献类型：
--
作者：
Huang Y;Harrison MR;Osorio A;Kim J;Baugh A;Duan C;Sucov HM;Lien CL
与哺乳动物的心脏不同，成年斑马鱼的心脏在严重损伤后能够完全再生。再生过程中最重要的事件之一是心肌细胞增殖，这会导致丢失的心肌被替换。在斑马鱼心脏再生过程中诱导心肌细胞增殖的生长因子仍有待确定。对心脏发育重要的信号通路可能会在心脏再生过程中被重新利用。最近显示 IGF2 对小鼠妊娠中期心脏发育期间的心肌细胞增殖和心脏生长很重要，尽管其在心脏再生中的作用尚不清楚。我们发现斑马鱼心脏再生过程中 igf2b 的表达上调。心室尖部切除后，在伤口、心内膜和心外膜中检测到 igf2b 表达，此时与心肌细胞增殖一致。表达显性负型 Igf1 受体 (dn-Igf1r) 的转基因斑马鱼胚胎的心肌细胞较少，心脏发育受损，用 Igf1r 抑制剂处理的胚胎也是如此。此外，抑制 Igf1r 信号传导可阻止心脏发育和再生过程中的心肌细胞增殖。我们发现 gata4:EGFP 标记的心肌细胞亚群需要 Igf 信号传导来促进再生区域。我们的研究结果表明 Igf 信号对于斑马鱼的心脏发育和心肌再生很重要。
Unlike its mammalian counterpart, the adult zebrafish heart is able to fully regenerate after severe injury. One of the most important events during the regeneration process is cardiomyocyte proliferation, which results in the replacement of lost myocardium. Growth factors that induce cardiomyocyte proliferation during zebrafish heart regeneration remain to be identified. Signaling pathways important for heart development might be reutilized during heart regeneration. IGF2 was recently shown to be important for cardiomyocyte proliferation and heart growth during mid-gestation heart development in mice, although its role in heart regeneration is unknown. We found that expression of igf2b was upregulated during zebrafish heart regeneration. Following resection of the ventricle apex, igf2b expression was detected in the wound, endocardium and epicardium at a time that coincides with cardiomyocyte proliferation. Transgenic zebrafish embryos expressing a dominant negative form of Igf1 receptor (dn-Igf1r) had fewer cardiomyocytes and impaired heart development, as did embryos treated with an Igf1r inhibitor. Moreover, inhibition of Igf1r signaling blocked cardiomyocyte proliferation during heart development and regeneration. We found that Igf signaling is required for a subpopulation of cardiomyocytes marked by gata4:EGFP to contribute to the regenerating area. Our findings suggest that Igf signaling is important for heart development and myocardial regeneration in zebrafish.
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心脏再生。
影响因子：
--
作者：
Choi, Wen-Yee;Poss, Kenneth D.
通讯作者：
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