LKB1IP promotes pathological cardiac hypertrophy by targeting PTEN/Akt signalling pathway.
LKB1IP promotes pathological cardiac hypertrophy by targeting PTEN/Akt signalling pathway.
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LKB1IP 通过靶向 PTEN/Akt 信号通路促进病理性心脏肥大。
DOI：
10.1111/jcmm.16199
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发表时间：
2021-03
影响因子：
5.3
通讯作者：
Zhang W
中科院分区：
文献类型：
--
作者：
Tian M;Jiang X;Li X;Yang J;Zhang C;Zhang W
病理性心脏肥大是全世界发病和死亡的主要原因。肝激酶 B1 相互作用蛋白 1 (LKB1IP) 被鉴定为肿瘤抑制因子 LKB1 的结合蛋白。然而，LKB1IP 在病理性心脏肥大发展中的作用尚未被探索。本研究的目的是探讨 LKB1IP 在心肌肥厚中对肥厚刺激的反应中的功能。我们研究了心力衰竭患者和异丙肾上腺素 (ISO) 或横主动脉缩窄 (TAC) 诱导的心脏肥大小鼠样本中 LKB1IP 的心脏水平。生成 LKB1IP 敲除小鼠并通过 ISO 注射或 TAC 手术进行攻击。然后检查心脏功能、肥厚和纤维化。在人和小鼠心脏样本中，LKB1IP 表达在肥厚刺激下显着上调。 LKB1IP 敲除显着保护小鼠心脏免受 ISO 或 TAC 诱导的心脏肥大和纤维化。 LKB1IP 过表达加剧了 ISO 诱导的心肌细胞肥大，而其抑制作用在体外减弱了肥大。从机制上讲，LKB1IP 通过直接靶向 PTEN 然后抑制其磷酸酶活性来激活 Akt 信号传导。总之，LKB1IP可能是病理性心脏肥大的潜在靶点。
Pathological cardiac hypertrophy represents a leading cause of morbidity and mortality worldwide. Liver kinase B1 interacting protein 1 (LKB1IP) was identified as the binding protein of tumour suppressor LKB1. However, the role of LKB1IP in the development of pathological cardiac hypertrophy has not been explored. The aim of this study was to investigate the function of LKB1IP in cardiac hypertrophy in response to hypertrophic stimuli. We investigated the cardiac level of LKB1IP in samples from patients with heart failure and mice with cardiac hypertrophy induced by isoproterenol (ISO) or transverse aortic constriction (TAC). LKB1IP knockout mice were generated and challenged with ISO injection or TAC surgery. Cardiac function, hypertrophy and fibrosis were then examined. LKB1IP expression was significantly up‐regulated on hypertrophic stimuli in both human and mouse cardiac samples. LKB1IP knockout markedly protected mouse hearts against ISO‐ or TAC‐induced cardiac hypertrophy and fibrosis. LKB1IP overexpression aggravated ISO‐induced cardiomyocyte hypertrophy, and its inhibition attenuated hypertrophy in vitro. Mechanistically, LKB1IP activated Akt signalling by directly targeting PTEN and then inhibiting its phosphatase activity. In conclusion, LKB1IP may be a potential target for pathological cardiac hypertrophy.
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