心肌肥厚过程中TGF-β和MAPK信号通路间的交互调节

Crosstalk between TGF-βand MAPK signaling pathways during cardiac hypertrophy

心肌肥厚是由于压力负荷增加、肌节蛋白突变、心肌梗死后心肌收缩力下调、神经体液因素改变等而引发的一种代偿性反应,其发病是一个漫长而复杂的过程,受多种细胞和因子的共同调节。转化生长因子(TGF)-β是纤维化形成的重要调节因子,参与心肌肥厚的形成。丝裂原活化蛋白激酶(MAPK)信号通路在细胞增殖、分化、凋亡和纤维化等过程中也发挥着重要作用。而TGF-β和MAPK信号通路之间存在交互调节,TGF-β通过非Smad途径调节MAPK信号通路,MAPK信号通路通过激活蛋白(AP)-1促进TGF-β激活,两通路之间共同靶点的深入研究可为心肌肥厚靶向治疗药物的研发提供思路。

Cardiac hypertrophy is a compensatory response that occurs due to overload-induced pressure,sarcomere protein mutation,down-regulation of myocardial contractility after myocardial infarction,changes of neurohumoral factors,and so on.The pathogenesis of cardiac hypertrophy is a long and complex process,which is regulated by a variety of cellular and molecular factors.Transforming growth factor(TGF)-βis an important regulator of fibrosis and participates in the formation of cardiac hypertrophy.Mitogen-activated protein kinase(MAPK)signaling pathway also plays an important role in the process of cell proliferation,differentiation,apoptosis and fibrosis.There is the crosstalk between TGF-βand MAPK signaling pathway.TGF-βregulates MAPK signaling pathway through non-Smad pathway,and MAPK signaling pathway promotes TGF-βactivation through activator protein(AP)-1,so the in-depth study of common targets between the two pathways can provide ideas for development of targeted drugs for cardiac hypertrophy.