丝裂原活化蛋白激酶1（MAPK1）通过磷脂酰肌醇-3激酶/蛋白激酶B（PI3K/AKT）信号通路上调转移相关肺腺癌转录本1（MALAT1）的表达，以促进心肌细胞增殖。
MAPK1 up-regulates the expression of MALAT1 to promote the proliferation of cardiomyocytes through PI3K/AKT signaling pathway.
作者信息
Zhao Jing, Li Li, Peng Ling
机构信息
Department of General Medicine, Sichuan Provincial Cancer Hospital Chengdu 610041, China.
出版信息
Int J Clin Exp Pathol. 2015 Dec 1;8(12):15947-53. eCollection 2015.
The previous studies identify mammalian heart is terminal differentiation organs without regenerative capacity. Recently, there is some evidence point that cardiomyocytes are not terminally differentiated cells and cell proliferation may be stimulated in the pathologic heart. The aim of this study is to discover the possible mechanism which involved in cardiomyocytes proliferation process. In this study, the proliferation assay and cell cycle assay showed the proliferation of cardiomyocytes was inhibited when the cells treated with MAPK1 inhibitor. Moreover, the bioinformatics analysis revealed MAPK1 was positively correlated with MALAT1. Meanwhile, the expression of MALAT1 in H9C2 cells with the treatment of MAPK1 siRNA was obvious lower than scramble siRNA treated group. Finally further study suggested H9C2 cells treated with Wortmannin in combination with LY294002 (PI3K/AKT signaling pathway inhibitor), the expression of MALAT1 was dramatically decreased. These results indicated that MAPK1 was able to increase the proliferation of cardiomyocytes via up-regulating the expression of MALAT1 through PI3K/AKT signaling pathway.
先前的研究表明哺乳动物心脏是终末分化器官，没有再生能力。最近，有一些证据表明心肌细胞不是终末分化细胞，并且在病理性心脏中细胞增殖可能会被刺激。本研究的目的是发现参与心肌细胞增殖过程的可能机制。在本研究中，增殖试验和细胞周期试验表明，当用MAPK1抑制剂处理细胞时，心肌细胞的增殖受到抑制。此外，生物信息学分析显示MAPK1与MALAT1呈正相关。同时，用MAPK1 siRNA处理的H9C2细胞中MALAT1的表达明显低于乱序siRNA处理组。最后进一步研究表明，用渥曼青霉素联合LY294002（PI3K/AKT信号通路抑制剂）处理H9C2细胞，MALAT1的表达显著降低。这些结果表明，MAPK1能够通过PI3K/AKT信号通路上调MALAT1的表达来增加心肌细胞的增殖。
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