Myocardin is differentially required for the development of smooth muscle cells and cardiomyocytes
Myocardin is differentially required for the development of smooth muscle cells and cardiomyocytes
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DOI：
10.1152/ajpheart.01192.2010
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发表时间：
2011-05-01
影响因子：
4.8
通讯作者：
Owens, Gary K.
中科院分区：
文献类型：
--
作者：
Hoofnagle, Mark H.;Neppl, Ronald L.;Owens, Gary K.
Hoofnagle MH，Neppl RL，Berzin EL，Teg Pipes GC，Olson EN，Wamhoff BW，Somlyo AV，Owens GK.肌钙蛋白是平滑肌细胞和心肌细胞发育所需的差异。Am J Physiol Heart Circ Physiol 300：H1707-H1721，2011.首次发表于2011年2月25日; doi：10.1152/ajpheart.01192.2010.-肌心素是一种血清反应因子（SRF）共激活剂，仅在心肌细胞和平滑肌细胞（SMC）中表达。然而，关于心肌素是否对这些细胞类型的正常分化至关重要，存在高度争议的证据，并且没有数据显示心脏或SMC亚型在发育过程中是否表现出不同的心肌素需求。本研究的结果显示，通过将心肌素（-/-）胚胎干细胞（ESC）注射到野生型（WT;即，心肌蛋白（+/+）ESC）囊胚。相比之下，心肌蛋白（-/-）ESC容易形成血管SMC，尽管与WT ESC相比频率降低。此外，心肌素（-/-）ESC与WT ESC在形成心房肌细胞方面竞争相等。使用我们实验室开发的独特的X射线微探针透射电子显微镜方法测定，心肌素（-/-）血管平滑肌细胞和心肌细胞的超微结构特征与WT对应物相比没有变化。在体外拟胚体SMC分化模型中，心肌素（-/-）ESC衍生的SMC也显示出正常的收缩特性，而不是受损的血栓素A2反应性。总之，这些结果提供了新的证据，心肌素是内脏SMC和心室肌细胞的发展，但在嵌合KO小鼠的设置心房肌细胞和血管SMC的发展是必不可少的。此外，结果表明，尚未确定的缺陷，在发展和/或成熟的心室心肌细胞可能有助于早期胚胎死亡观察到的常规myocardin基因敲除小鼠和观察到的缺陷，在发展中的血管平滑肌细胞可能是继发于这些缺陷。
Hoofnagle MH, Neppl RL, Berzin EL, Teg Pipes GC, Olson EN, Wamhoff BW, Somlyo AV, Owens GK. Myocardin is differentially required for the development of smooth muscle cells and cardiomyocytes. Am J Physiol Heart Circ Physiol 300: H1707-H1721, 2011. First published February 25, 2011; doi:10.1152/ajpheart.01192.2010.-Myocardin is a serum response factor (SRF) coactivator exclusively expressed in cardiomyocytes and smooth muscle cells (SMCs). However, there is highly controversial evidence as to whether myocardin is essential for normal differentiation of these cell types, and there are no data showing whether cardiac or SMC subtypes exhibit differential myocardin requirements during development. Results of the present studies showed the virtual absence of myocardin(-/-) visceral SMCs or ventricular myocytes in chimeric myocardin knockout (KO) mice generated by injection of myocardin(-/-) embryonic stem cells (ESCs) into wild-type (WT; i.e., myocardin(+/+) ESC) blastocysts. In contrast, myocardin(-/-) ESCs readily formed vascular SMC, albeit at a reduced frequency compared with WT ESCs. In addition, myocardin(-/-) ESCs competed equally with WT ESCs in forming atrial myocytes. The ultrastructural features of myocardin(-/-) vascular SMCs and cardiomyocytes were unchanged from their WT counterparts as determined using a unique X-ray microprobe transmission electron microscopic method developed by our laboratory. Myocardin(-/-) ESC-derived SMCs also showed normal contractile properties in an in vitro embryoid body SMC differentiation model, other than impaired thromboxane A2 responsiveness. Together, these results provide novel evidence that myocardin is essential for development of visceral SMCs and ventricular myocytes but is dispensable for development of atrial myocytes and vascular SMCs in the setting of chimeric KO mice. In addition, results suggest that as yet undefined defects in development and/or maturation of ventricular cardiomyocytes may have contributed to early embryonic lethality observed in conventional myocardin KO mice and that observed deficiencies in development of vascular SMC may have been secondary to these defects.