药学学报, 2021, 56(11): 2923-2933
引用本文:
顾璇, 程明涵, 高建*. AMPK在纤维化疾病中的多重作用[J]. 药学学报, 2021, 56(11): 2923-2933.
GU Xuan, CHENG Ming-han, GAO Jian*. The multiple roles of AMPK in fibrotic diseases[J]. Acta Pharmaceutica Sinica, 2021, 56(11): 2923-2933.

AMPK在纤维化疾病中的多重作用
顾璇, 程明涵, 高建*
上海交通大学医学院附属上海儿童医学中心, 上海 200120
摘要:
纤维化是导致器官损伤和衰竭的常见表现。根据美国相关统计资料显示,因纤维化疾病所引起的死亡占该国所有死亡人数的45%。因此,纤维化疾病受到世界范围内的广泛关注。作为体内调节能量代谢平衡的关键激酶—腺苷酸活化蛋白激酶 (AMP-activated protein kinase,AMPK),主要控制细胞从合成代谢到分解代谢的转化,并通过磷酸化其底物来恢复能量平衡,因此它成为糖尿病和其他代谢相关疾病的治疗核心;近期大量病理学研究显示纤维化组织中AMPK的表达与正常组织相比呈现明显下调,且激活AMPK可以改善多种纤维化病理进程 (包括自噬功能障碍、氧化应激、成纤维细胞增殖、上皮-间质转化、成纤维细胞向肌成纤维细胞分化等)。因此,本综述将基于AMPK的结构和功能及其对纤维化疾病重要表型的作用展开讨论,为AMPK成为纤维化的重要防治靶点提供证据。
关键词:    AMPK      纤维化      自噬      氧化应激      成纤维细胞增殖      上皮-间质转化      成纤维细胞向肌成纤维细胞分化     
The multiple roles of AMPK in fibrotic diseases
GU Xuan, CHENG Ming-han, GAO Jian*
Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200120, China
Abstract:
Fibrosis is a common manifestation of organ damage and failure. According to relevant statistics in the United States, deaths caused by fibrotic diseases account for 45% of all deaths in the country. Therefore, fibrotic diseases have received widespread attention worldwide. As a key kinase that regulates energy balance, AMP-activated protein kinase (AMPK), which mainly controls the transformation of cells from anabolic to catabolism, and restores the energy balance by phosphorylating its substrates. Therefore, it has become the core of treatment for diabetes and other metabolic-related diseases. Numerous recent pathological studies have shown that the expression of AMPK in fibrotic tissues is significantly down-regulated compared with normal tissues, and activation of AMPK could improve various fibrotic pathological processes (including autophagy dysfunction, oxidative stress, fibroblast proliferation, epithelial-mesenchymal transition, fibroblast-to-myofibroblast differentiation). Therefore, this review will discuss the structure and function of AMPK and its role in important phenotypes of fibrotic diseases, and provide evidence for AMPK as an important target for prevention and treatment of fibrosis.
Key words:    AMPK    fibrosis    autophagy    oxidative stress    fibroblast proliferation    epithelial-mesenchymal transition    fibroblast-to-myofibroblast differentiation   
收稿日期: 2021-06-28
DOI: 10.16438/j.0513-4870.2021-0960
基金项目: 国家自然科学基金资助项目(81973637,81473267,81274172);国家中医药管理局青年歧黄学者支持项目.
通讯作者: 高建,Tel:86-431-88782482,E-mail:gaojianayfy@163.com
Email: gaojianayfy@163.com
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