MEF2 is upregulated during cardiac hypertrophy and is required for normal post-natal growth of the myocardium
MEF2 is upregulated during cardiac hypertrophy and is required for normal post-natal growth of the myocardium
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DOI：
10.1016/s0960-9822(00)80027-5
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发表时间：
1999-10-21
期刊：
影响因子：
9.2
通讯作者：
Megeney, LA
中科院分区：
文献类型：
--
作者：
Kolodziejczyk, SM;Wang, L;Megeney, LA
在哺乳动物中，胎儿心脏的生长受心肌细胞增殖的调节。在出生前生命的后期阶段，这种增殖显著减少[1，2]，并且在向成年过渡期间心脏大小的急剧扩张完全是由于个体心肌细胞的肥大[3-5]，心肌细胞肥大也有助于大多数出生后心脏病的病理[6-10]，在这种情况下，许多信号转导途径被认为是效应子和改变的心脏基因表达之间的联系[11-16]。然而，一个共同的途径尚未被发现。在此，我们发现在两种类型的心肌细胞肥大中，应激激活的激酶p38的活性增强，我们还发现激活的p38激酶的靶点是心脏转录因子MEF 2，表达显性负性形式的MEF 2C的转基因小鼠显示心肌的出生后生长减弱。这些结果提供了第一个证据，一个单一的途径调节正常和病理性心肌细胞肥大。
In mammals, growth of the fetal heart is regulated by proliferation of cardiac muscle cells. At later stages of pre-natal life, this proliferation diminishes profoundly [1,2] and the dramatic expansion in heart size during the transition to adulthood is due exclusively to hypertrophy of individual cardiomyocytes [3-5], Cardiomyocyte hypertrophy also contributes to the pathology of most post-natal heart disease [6-10], Within this context, numerous signal transduction pathways have been implicated as the link between the effector(s) and altered cardiac gene expression [11-16]. A common pathway has yet to be discovered, however. Here, we found that the activity of the stress-activated kinase p38 was enhanced in both types of cardiomyocyte hypertrophy, We also found that a target of the activated p38 kinase is the cardiac transcription factor MEF2, Transgenic mice expressing a dominant negative form of MEF2C displayed attenuated post-natal growth of the myocardium. These results provide the first evidence for a single pathway regulating both normal and pathologic cardiomyocyte hypertrophy.