PI3K/Akt/mTOR通路与自噬在类风湿关节炎滑膜细胞增生中的意义

doi:10.3969/j.issn.1674-490X.2013.05.019

摘要/Abstract

摘要： 细胞自噬是生物体生长发育中极为关键的自救行为，在应激状态下，通过清除细胞内变性蛋白及坏死物质，重建结构，维持细胞生存，但过度的自噬则会引起细胞的Ⅱ型凋亡。PI3K/Akt/mTOR是广泛存在于多种细胞内的一条重要信号通路，参与体内多种生理病理过程，其活化后对细胞自噬有抑制作用。在类风湿关节炎发病的早期，滑膜成纤维细胞（RASF）可通过多种途径启动自噬，维持RASF细胞内环境的稳定和细胞增生，随着病情的进展，血小板活化颗粒如PDGFRα等释放后可通过激活RASF中的PI3K/Akt/mTOR信号通路抑制自噬，从而避免RASF因过度自噬而诱导的Ⅱ型细胞凋亡，使滑膜细胞持续增生，加重RA的病情。本文旨在对PI3K/Akt/mTOR信号通路与自噬影响RA滑膜细胞持续增生的意义进行综述，以期探讨RA的发病机制、寻找新的治疗靶点。

关键词: 自噬, Ⅱ型细胞凋亡, P13K/Akt/mTOR, RASF, 血小板活化颗粒

Abstract: Autophagy is a crucial self-saving behavior of mammalian cells in growth and development of organism. Autophagy can keep cells survival via eliminating the metaprotein and necrosis substance then rebuilding the structure of cells in the situation of stress, but it can also lead to typeⅡapoptosis if it occur unduly. PI3K/Akt/mTOR , which involved in multiple physiological and pathological process, is an important signal pathway existing in various cells. The products of activated PI3K/Akt/mTOR pathway will inhibit the cell autophagy. In the early stage of rheumatoid arthritis (RA), the rheumatoid arthritis synovial ifbroblasts (RASF) initiate autophagy in several ways, in order to maintaining the homeostasis of RASF and cell proliferation. With the progress of RA, the activating platelet particles (such as PDGFRα) will suppress autophagy via activating the PI3K/Akt/mTOR signal pathway, thereby prevent RASF from typeⅡapoptosis induced by excessive autophagy, lead to RASF’s continuing proliferation and aggravate the pathogenetic condition. The purpose of this article is to summarize the signiifcance of PI3K/Akt/mTOR signal pathway and autophagy in the persistently proliferation of RASF, discuss the pathogenesis of RA and ifnd new therapeutic targets.

Key words: autophagy, typeⅡapoptosis, PI3K/Akt/mTOR, RASF, activating platelet particles

中图分类号:

孟明,梁红格,方皓,周蕾,冯建勇,董阳,闫振,陈冬志. PI3K/Akt/mTOR通路与自噬在类风湿关节炎滑膜细胞增生中的意义[J]. 医学研究与教育, 2013, 30(5): 69-74.

MENG Ming,LIANG Hongge,FANG Hao,ZHOU Lei,FENG Jianyong,DONG Yang,YAN Zhen,CHEN Dongzhi. The significance of PI3K/Akt/mTOR pathway and autophagy in the proliferation of synovial cells in rheumatoid arthritis[J]. Medical Reserch and Education, 2013, 30(5): 69-74.

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