FIBROBLAST GROWTH-FACTOR RECEPTOR IS REQUIRED FOR IN-VIVO CARDIAC MYOCYTE PROLIFERATION AT EARLY EMBRYONIC STAGES OF HEART DEVELOPMENT
FIBROBLAST GROWTH-FACTOR RECEPTOR IS REQUIRED FOR IN-VIVO CARDIAC MYOCYTE PROLIFERATION AT EARLY EMBRYONIC STAGES OF HEART DEVELOPMENT
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DOI：
10.1073/pnas.92.2.467
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发表时间：
1995-01-17
影响因子：
11.1
通讯作者：
MIKAWA, T
中科院分区：
文献类型：
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作者：
MIMA, T;UENO, H;MIKAWA, T
在鸟类和哺乳动物中，心肌细胞在新生期终止有丝分裂活动，成年心脏心肌损伤后不发生心肌再生。即使是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失去有丝分裂活性。几种生长因子，包括成纤维细胞生长因子（FGF），已被证明在胚胎心脏和一些已被证明会影响培养中的肌细胞终末分化，然而，这些生长因子都没有被证明能重新激活有丝分裂后的肌细胞的细胞分裂，也没有令人满意的定义其在体内的功能。为了阐明FGF信号传导在心脏生长中的作用，我们制备了两种逆转录病毒载体，其能够抑制（i）具有1型受体（FGFR 1）的显性负突变体的FGF受体（FGFR）的功能或（ii）通过转录内源性FGFR 1的反义RNA来翻译内源性FGFR 1，两种载体均抑制心肌细胞增殖和/或或在鸡胚胎发育的第一周期间存活，但在第二周后效果小得多。在过表达全长FGFR 1后没有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信号调节心肌细胞的生长在管状阶段的心脏，但心肌细胞的生长成为FGF独立的胚胎发生后的第二周。
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.