Open AccessLKB1 suppression promotes cardiomyocyte regeneration via LKB1-AMPK-YAP axis
Author(s) -
Shuang Qu,
Qiao Liao,
Cheng Yu,
Yue Chen,
Han Luo,
Xinhui Xia,
Duofen He,
Zaicheng Xu,
Pedro A. José,
Zhuxin Li,
Wei Eric Wang,
Qing Lyu,
Chunyu Zeng
Publication year - 2022
Publication title -
bosnian journal of basic medical sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.738
H-Index - 25
eISSN - 1840-4812
pISSN - 1512-8601
DOI - 10.17305/bjbms.2021.7225
Subject(s) - ampk , microbiology and biotechnology , protein kinase a , gene knockdown , cell growth , regeneration (biology) , amp activated protein kinase , medicine , kinase , effector , biology , apoptosis , biochemistry
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.