mTOR通路与自噬在类风湿关节炎滑膜细胞增生中的意义被引量：16

The significance of PI3K/Akt/mTOR pathway and autophagy in the proliferation of synovial cells in rheumatoid arthritis

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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。 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 type Ⅱ apoptosis 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 fibroblasts （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 PDGFRet） will suppress autophagy via activating the PI3K/Akt/mTOR signal pathway, thereby prevent RASF from type I apoptosis induced by excessive autophagy, lead to RASF＇s continuing proliferation and aggravate the pathogenetic condition. The purpose of this article isto summarize the significance of PI3K/Akt/mTOR signal pathway and autophagy in the persistently proliferation of RASF, discuss the pathogenesis of RA and find new therapeutic targets.

作者孟明梁红格方皓周蕾冯建勇董阳闫振陈冬志

机构地区河北大学基础医学院

出处《医学研究与教育》 CAS 2013年第5期69-74,共6页 Medical Research and Education

基金河北省医学科学研究重点课题(20100450) "十一五"全军中医药重大临床攻关课题(2006011003) 河北大学研究生教育教学改革重点项目(YJ11-10)

关键词自噬 Ⅱ型细胞凋亡 P13K Akt MTOR RASF 血小板活化颗粒 autophagy type Ⅱ apoptosis PI3K/Akt/mTOR RASF activating platelet particles

分类号 R3 [医药卫生—基础医学]

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1PRETORIUS E, OBERHOLZER H M, SPUY W J, et al. Scanning electron microscopy of fibrin networks in rheumatoid arthritis: a qualitative analysis[J]. Rheumatol Int, 2012, 32(6): 1611-1615.
2SMITH H S, BRACKEN D, SMITH J M, et al. Painful rheumatoid arthritis[J]. Pain Physician, 2011, 14(5): 427-458.
3ERIC B E, NIGROVIC P A, LARABEE K, et al. Platelets amplify inflammation in arthritis via collagen-dependent microparticle production[J]. Science, 2010, 26(20): 322-340.
4LIU K W, FENG H, BACHOO R, et al. SHP-2/PTPN11 mediates gliomagenesis driven by PDGFRA and INK4A/ARF aberrations in mice and humans[J]. Clin Invest, 2011,121(3): 905-921.
5ZAMANI A, QU Z. Serotonin activates angiogenic phosphorylation signaling in human endothelial cells[J]. FEBS Lett, 2012, 586(16): 2360-2364.
6MITRA A, RAYCHAUDHURI S K, RAYCHAUDHURI S P. IL-22 induced cell proliferation is regulated by PI3K/Akt/mTOR signaling cascade[J]. Cytokine, 2012, 60(1): 38-42.
7REEDQUIST K A, LUDIKHUIZE J, TAK P P. Phosphoinositide 3-kinase signalling and FoxO transcription factors in rheumatoid arthritis[J]. Biochem Soc Trans, 2006, 34(5): 727-730.
8WU T, MOHAN C. The AKT axis as a therapeutic target in autoimmune diseases[J]. Endocr Metab Immune Disord Drug Targets, 2009, 9(2): 145-50.
9GAO N, ZHANG Z, JIANG B H, et al. G1 cell cycle progression and the expression of Glcyclins are regulated by PI3K/AKT/Mtor/ p70s6kl signaling in human ovarian cancer cells[J]. Am J Physiol Cell Physiol, 2004, 287(2): 281-291.
10SUN H, WANG Z, YAKISICH J S. Natural Products Targeting Autophagy via the PI3K/Akt/mTOR Pathway as Anticancer Agents[J]. Anticancer Agents Med Chem, 2012, 13(7): 1048-1056.