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LKB1 suppression promotes cardiomyocyte regeneration via LKB1-AMPK-YAP axis.
Biomolecules and Biomedicine ( IF 3.1 ) Pub Date : 2022-04-29 , DOI: 10.17305/bjbms.2021.7225
Shuang Qu 1 , Qiao Liao 1 , Cheng Yu 1 , Yue Chen 1 , Han Luo 1 , Xuewei Xia 1 , Duofen He 1 , Zaicheng Xu 1 , Pedro A Jose 2 , Zhuxin Li 1 , Wei Eric Wang 1 , Qing Rex Lyu 3 , Chunyu Zeng 4
Affiliation  

The regenerative potential of cardiomyocytes in adult mammals is limited. Previous studies reported that cardiomyocyte proliferation is suppressed by AMP-activated protein kinase (AMPK). The role of liver kinase B1 (LKB1), as the major upstream kinase for AMPK, on cardiomyocyte proliferation is unclear. In this study, we found that the LKB1 levels rapidly increased after birth. With loss- and gain-of-function study, our data demonstrated that LKB1 levels negatively correlate with cardiomyocyte proliferation. We next identified Yes-associated protein (YAP) as the downstream effector of LKB1 using high-throughput RNA sequencing. Our results also demonstrated that AMPK plays an essential role in Lkb1 knockdown-induced cardiomyocyte proliferation. Importantly, deactivated AMPK abolished the LKB1-mediated regulation of YAP nuclear translocation and cardiomyocyte proliferation. Thus, our findings suggested the role of LKB1-AMPK-YAP axis during cardiomyocyte proliferation, which could be used as a potential target for inducing cardiac regeneration after injury.

中文翻译:

LKB1 抑制通过 LKB1-AMPK-YAP 轴促进心肌细胞再生。

成年哺乳动物心肌细胞的再生潜力是有限的。先前的研究报道,AMP 活化蛋白激酶 (AMPK) 抑制心肌细胞增殖。作为 AMPK 的主要上游激酶,肝激酶 B1 (LKB1) 在心肌细胞增殖中的作用尚不清楚。在这项研究中,我们发现 LKB1 水平在出生后迅速增加。通过功能丧失和获得研究,我们的数据表明 LKB1 水平与心肌细胞增殖呈负相关。我们接下来使用高通量 RNA 测序将 Yes 相关蛋白 (YAP) 确定为 LKB1 的下游效应子。我们的研究结果还表明,AMPK 在 Lkb1 敲低诱导的心肌细胞增殖中起重要作用。重要的,失活的 AMPK 消除了 LKB1 介导的 YAP 核易位和心肌细胞增殖的调节。因此,我们的研究结果表明 LKB1-AMPK-YAP 轴在心肌细胞增殖过程中的作用,可作为诱导损伤后心脏再生的潜在靶点。
更新日期:2022-04-29
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