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生长分化因子-15在神经系统、心血管疾病以及癌症进程中的作用

刘冬冬, 梅岩艾^*

复旦大学生命科学学院，上海 200433

摘要

生长分化因子-15 (growth differentiation factor-15, GDF-15)是转化生长因子-β (transforming growth factor beta, TGF-β)超家族中的一员。GDF-15的表达量通常会随着脑组织损伤、癌症、心血管疾病以及炎症反应等组织病理性损伤而有显著的升高，使其成为一个潜在的疾病生物标志蛋白。近期有研究表明GDF-15在神经系统中具有一定的神经营养作用，而最新研究揭示GDF-15具有调制神经元离子通道的表达、影响突触传递功能的作用。在癌症以及心血管系统中，GDF-15也参与了多种复杂的调控机制。本文对GDF-15的表达调控、作用机制以及主要的病理生理学作用进行介绍，探讨GDF-15的生物活性以及其在基础研究和临床应用中的价值。

关键词： 生长分化因子-15; 信号通路; 神经系统 ; 癌症 ; 心血管系统

分类号：Q426;R363

Effects of growth differentiation factor-15 (GDF-15) on neurological systems, cardiovascular diseases, and cancer progression

LIU Dong-Dong, MEI Yan-Ai^*

School of Life Sciences, Fudan University, Shanghai 200433, China

Abstract

Growth differentiation factor-15 (GDF-15) is a member of the transforming growth factor beta superfamily. GDF-15 expression is dramatically upregulated during acute brain injury, cancer, cardiovascular disease, and inflammation, suggesting its potential value as a disease biomarker. It has been suggested that GDF-15 has neurotropic effects in the nervous system. Our studies showed that GDF-15 modulated the expression of neuronal K+ and Ca2+ ion channels and increased the release of excitatory transmitter in the medial prefrontal cortex of mice. GDF-15 is also involved in the complex modulation of cancer and cardiovascular disease. Here, we reviewed studies involving the modulation of GDF-15 expression and its mechanisms, the primary pathological and physiological functions of GDF-15 in neurological and cardiovascular systems, and its role in cancer progression. The biological effects and the values of GDF-15 in basic research and clinical applications were also addressed.

Key words: growth differentiation factor-15; signaling pathway; nervous system ; cancer ; cardiovascular system

收稿日期：2016-07-11　　录用日期：2016-10-09

通讯作者：梅岩艾　　E-mail: yamei@fudan.edu.cn

引用本文：

刘冬冬, 梅岩艾. 生长分化因子-15在神经系统、心血管疾病以及癌症进程中的作用[J]. 生理学报 2017; 69 (1): 109-121.

LIU Dong-Dong, MEI Yan-Ai. Effects of growth differentiation factor-15 (GDF-15) on neurological systems, cardiovascular diseases, and cancer progression. Acta Physiol Sin 2017; 69 (1): 109-121 (in Chinese with English abstract).