Myostatin regulates cardiomyocyte growth through modulation of Akt signaling
Myostatin regulates cardiomyocyte growth through modulation of Akt signaling
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DOI：
10.1161/01.res.0000231290.45676.d4
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发表时间：
2006-07-07
影响因子：
20.1
通讯作者：
Rosenzweig, Anthony
中科院分区：
文献类型：
--
作者：
Morissette, Michael R.;Cook, Stuart A.;Rosenzweig, Anthony
肌生长抑制素是一种高度保守的、有效的骨骼肌肥厚负调节因子，适用于从啮齿动物到人类的许多物种，尽管其作用机制尚不完全清楚。来自心脏肥厚遗传模型的心脏转录谱分析揭示了肌生长抑制素的急剧上调，这在以前没有被认识到在心脏中起作用。本研究表明，肌生长抑制素通过抑制p38和丝氨酸-苏氨酸激酶Akt（从果蝇到哺乳动物的许多物种的细胞大小的关键决定因素）来消除体外对苯肾上腺素的心肌细胞生长反应。对雄性肌抑制素缺失小鼠的评估显示，它们的心肌细胞和心脏在基线时比对照组略小，但在慢性苯肾上腺素输注后表现出更旺盛的生长。苯肾上腺素处理后，肌生成抑制素缺失小鼠心脏生长的增加与体内p38磷酸化和Akt活化的增加相对应。总之，这些数据表明，肌肉生长抑制素在心脏中是动态调节的，其作用比以前认识到的更广泛，可以调节多种类型横纹肌的生长。
Myostatin is a highly conserved, potent negative regulator of skeletal muscle hypertrophy in many species, from rodents to humans, although its mechanisms of action are incompletely understood. Transcript profiling of hearts from a genetic model of cardiac hypertrophy revealed dramatic upregulation of myostatin, not previously recognized to play a role in the heart. Here we show that myostatin abrogates the cardiomyocyte growth response to phenylephrine in vitro through inhibition of p38 and the serine - threonine kinase Akt, a critical determinant of cell size in many species from drosophila to mammals. Evaluation of male myostatin-null mice revealed that their cardiomyocytes and hearts overall were slightly smaller at baseline than littermate controls but exhibited more exuberant growth in response to chronic phenylephrine infusion. The increased cardiac growth in myostatin-null mice corresponded with increased p38 phosphorylation and Akt activation in vivo after phenylephrine treatment. Together, these data demonstrate that myostatin is dynamically regulated in the heart and acts more broadly than previously appreciated to regulate growth of multiple types of striated muscle.