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转化生长因子-β激活激酶1在病理性心肌肥大中的作用研究进展

李莹, 陈越, 张冬梅^*

大连医科大学生理学教研室，大连 116044

摘要

转化生长因子-β激活激酶1 (transforming growth factor-β-activated kinase 1, TAK1)是促分裂原活化蛋白激酶激酶激酶(mitogen-activated protein kinase kinase kinase, MAPKKK)家族的成员之一，参与调节一些重要的生物功能。心肌肥大分为生理性心肌肥大和病理性心肌肥大，它们的发生机制和蛋白表达不同。TAK1既参与正常心肌的发育，也在调节病理性心肌肥大发生和发展中发挥着重要的作用。血管紧张素II (angiotensin II, AngII)或压力负荷通过不同的方式，如经低氧诱导因子-1α(hypoxia-inducible factor-1α, HIF-1α)促进TAK1转录和表达，或经转化生长因子-β1 (transforming growth factor-β1, TGF-β1)、甲状腺激素及泛素蛋白酶等促进TAK1磷酸化或泛素化，诱导病理性心肌肥大。本文就TAK1在病理性心肌肥大发生和发展中的作用进行综述，为临床心肌肥大的防治提供重要策略和潜在靶点。

关键词： 转化生长因子-β激活激酶1; 心肌肥大; 信号通路

分类号：R332;R363.2;R329.2

Transforming growth factor-β-activated kinase 1 and pathological myocardial hypertrophy

LI Ying, CHEN Yue, ZHANG Dong-Mei^*

Department of Physiology, Dalian Medical University, Dalian 116044, China

Abstract

The transforming growth factor-β-activated kinase 1 (TAK1) is a member of the mitogen-activated protein kinase kinase kinase (MAPKKK) family. TAK1 plays important roles in many biological functions. Cardiac hypertrophy can be identified as physiological or pathological myocardial hypertrophy. TAK1 not only participates in the development of normal myocardium, but also plays an important role in regulating the occurrence and development of pathological myocardial hypertrophy. Angiotensin II (Ang II) or pressure overload induces pathological cardiac hypertrophy through different ways, such as hypoxia-inducible factor-1α (HIF-1α)-mediated transcriptional expression of TAK1, or transforming growth factor-β1 (TGF-β1)-, thyroid hormone-, ubiquitin protease-mediated TAK1 phosphorylation or ubiquitination. This article reviews the role of TAK1 in the occurrence and development of pathological myocardial hypertrophy and discusses the potential of TAK1 as an important target for the prevention and treatment of clinical myocardial hypertrophy.

Key words: transforming growth factor-β-activated kinase 1; cardiac hypertrophy; signaling pathway

收稿日期：2019-08-09　　录用日期：2020-02-13

通讯作者：张冬梅　　E-mail: dongmeizhang72@163.com

DOI: 10.13294/j.aps.2020.0048

引用本文：

李莹, 陈越, 张冬梅. 转化生长因子-β激活激酶1在病理性心肌肥大中的作用研究进展[J]. 生理学报 2020; 72 (4): 499-505.

LI Ying, CHEN Yue, ZHANG Dong-Mei. Transforming growth factor-β-activated kinase 1 and pathological myocardial hypertrophy. Acta Physiol Sin 2020; 72 (4): 499-505 (in Chinese with English abstract).