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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Fibroblast growth factor receptor is required for in vivo cardiac myocyte proliferation at early embryonic stages of heart development.
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Fibroblast growth factor receptor is required for in vivo cardiac myocyte proliferation at early embryonic stages of heart development.

机译：成纤维细胞生长因子受体是心脏发育早期胚胎阶段体内心肌细胞增殖所必需的。

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摘要

In birds and mammals, cardiac myocytes terminate mitotic activity in the neonatal period and regeneration of cardiac muscle does not occur after myocardial injury in adult hearts. Even embryonic myocytes, which actively proliferate in vivo, quickly lose mitotic activity when placed in cell culture. Several growth factors, including fibroblast growth factor (FGF), have been documented in embryonic hearts and some have been shown to influence myocyte terminal differentiation in culture. However, none of these growth factors have been shown to reactivate cell division in postmitotic myocytes nor have their in vivo functions been defined satisfactorily. To clarify the role of FGF signaling in heart growth, we prepared two retroviral vectors capable of suppressing (i) functions of FGF receptors (FGFRs) with a dominant-negative mutant of receptor type 1 (FGFR1) or (ii) the translation of endogenous FGFR1 by transcribing its antisense RNA. Both vectors inhibited myocyte proliferation and/or survival during the first week of chicken embryonic development but had much less effect after the second week. No apparent alteration of myocyte growth was observed after overexpression of full-length FGFR1. These results suggest that receptor-coupled FGF signaling regulates cardiac myocyte growth during tubular stages of cardiogenesis but that myocyte growth becomes FGF-independent after the second week of embryogenesis.
机译：在鸟类和哺乳动物中，心肌细胞在新生儿期终止有丝分裂活动，成年心脏心肌损伤后不会发生心肌再生。甚至在体内活跃增殖的胚胎肌细胞，当置于细胞培养物中时也会迅速丧失有丝分裂活性。在胚胎心脏中已经记录了几种生长因子，包括成纤维细胞生长因子（FGF），并且已经表明一些生长因子会影响培养物中肌细胞的终末分化。但是，这些生长因子均未显示可在有丝分裂后的心肌细胞中重新激活细胞分裂，也未令人满意地定义其体内功能。为了阐明FGF信号在心脏生长中的作用，我们制备了两种逆转录病毒载体，它们能够抑制（i）具有受体1型显性阴性突变体（FGFR1）的FGF受体（FGFRs）的功能或（ii）内源性翻译FGFR1转录其反义RNA。两种载体均在鸡胚胎发育的第一周内抑制了肌细胞的增殖和/或存活，但在第二周后效果却差得多。全长FGFR1过表达后未观察到肌细胞生长的明显改变。这些结果表明，受体偶联的FGF信号传导在心脏发生的管状阶段调节心肌细胞的生长，但是在胚胎发生的第二周后，心肌细胞的生长变得与FGF无关。

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