LKB1 suppression promotes cardiomyocyte regeneration via LKB1-AMPK-YAP axis

The regenerative potential of cardiomyocytes in adult mammals is limited. The 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.

Automated summary

The regenerative potential of cardiomyocytes in adult mammals is limited. This study discovered that liver kinase B1 (LKB1) negatively regulates cardiomyocyte proliferation and identified Yes-associated protein (YAP) as its downstream effector. Moreover, AMPK plays a crucial role in the LKB1-mediated regulation of cardiomyocyte proliferation. These findings suggest the involvement of the LKB1-AMPK-YAP axis in cardiomyocyte proliferation and its potential as a target for cardiac regeneration.