[1]孙明慧,吴 虹,卜妍红,等.介导缺氧诱导因子-1α表达的相关信号通路在类风湿性关节炎中的研究进展[J].中国药理学通报,2019,(09):1197-1202.[doi:10.3969/j.issn.1001-1978.2019.09.004]
 SUN Ming-hui,WU Hong,BU Yan-hong,et al.Research progress of signaling pathways involved in expression of hypoxia-inducible factor-1α in rheumatoid arthritis[J].Chinese Pharmacological Bulletin,2019,(09):1197-1202.[doi:10.3969/j.issn.1001-1978.2019.09.004]
点击复制

介导缺氧诱导因子-1α表达的相关信号通路在类风湿性关节炎中的研究进展()
分享到:

《中国药理学通报》[ISSN:/CN:]

卷:
期数:
2019年09期
页码:
1197-1202
栏目:
讲座与综述
出版日期:
2019-09-09

文章信息/Info

Title:
Research progress of signaling pathways involved in expression of hypoxia-inducible factor-1α in rheumatoid arthritis
文章编号:
1001-1978(2019)09-1197-06
作者:
孙明慧吴 虹卜妍红张 衡戴学静王 言占 翔
安徽中医药大学药学院,新安医学教育部重点实验室,中药复方安徽省重点实验室,安徽 合肥 230012
Author(s):
SUN Ming-hui WU Hong BU Yan-hong ZHANG Heng DAI Xue-jing WANG Yan ZHAN Xiang
School of Pharmacy, Anhui University of Chinese Medicine; Key Lab of Xin'an Medicine, Ministry of Education; Anhui Province Key Lab of Chinese Medicinal Formula, Hefei 230012, China
关键词:
类风湿性关节炎 缺氧微环境 缺氧诱导因子1α 信号通路 作用机制 炎症
Keywords:
rheumatoid arthritis hypoxia microenvironment hypoxia-inducible factor-1α signaling pathway mechanism inflammation
分类号:
R329.2; R364.5; R394; R593.22; R845.22; R977.6
DOI:
10.3969/j.issn.1001-1978.2019.09.004
文献标志码:
A
摘要:
类风湿性关节炎(rheumatoid arthritis, RA)是一种系统性自身免疫性疾病,其病情的发生发展与关节缺氧微环境密切相关。缺氧诱导因子1α(hypoxia-inducible factor-1α, HIF-1α)是调节细胞对缺氧反应的核转录因子,在促进滑膜炎症、血管新生及血管翳形成、软骨破坏及骨侵蚀方面发挥重要作用。HIF-1α的表达除受氧感受器调节外,还受多条信号转导途径的调控,包括PI3K/Akt、Ras-Raf-MEK-ERK、JAK/STAT、NF-κB等。该文就参与调控HIF-1α表达的信号通路进行概述,以期为治疗RA以及寻找新的改善病情药物提供新的思路和依据。
Abstract:
Rheumatoid arthritis(RA)is a systemic autoimmune disease whose development is closely related to the hypoxic microenvironment of joints.Hypoxia-inducible factor-1α(HIF-1α)is a nuclear transcription factor that regulates cellular responses to hypoxia and plays an important role in promoting synovial inflammation, angiogenesis, pannus formation, cartilage destruction and bone erosion.In addition to regulation by oxygen receptors, its expression is regulated by multiple signal transduction pathways, including PI3K/Akt, Ras-Raf-MEK-ERK, JAK/STAT and NF-κB, etc.This article provides an overview of the signaling pathways involved in the regulation of HIF-1α expression, in order to provide new ideas and evidence for the treatment of RA and the search for new disease modifying antirheumatic drugs.

参考文献/References:

[1] Firestein G S, McInnes I B.Immunopathogenesis of rheumatoid arthritis[J].Immunity, 2017,46(2):183-96.
[2] 于若寒, 赵金霞, 刘湘源.低氧诱导因子在类风湿关节炎发病机制中的作用[J].北京大学学报(医学版), 2016, 48(6):1095-9.
[2] Yu R H, Zhao J X, Liu X Y.Role of hypoxia-inducible factor in the pathogenesis of rheumatoid a rthritis[J].J Peking Univ(Health Sci), 2016, 48(6): 1095-9.
[3] Xu J, Feng Z, Chen S, et al.Taxol alleviates collagen-induced arthritis in mice by inhibiting the formation of microvessels[J].Clin Rheumatol, 2019, 38(1):19-27.
[4] 李 梦, 钱海兵.铁筷子醇提物对佐剂性关节炎大鼠HIF-1α、VEGF和MMP-3表达的影响[J].中国药理学通报, 2016, 32(9): 1326-7.
[4] Li M, Qian H B.Effects of alcohol extract from root of wintersweet on expression of HIF-1α,VEGF and MMP-3 in adjuvant arthritis rats[J].Chin Pharmacol Bull, 2016, 3232(9): 1326-7.
[5] Li G, Qin Y, Du P.Andrographolide inhibits the migration, invasion and matrix metalloproteinase expression of rheumatoid arthritis fibroblast-like synoviocytes via inhibition of HIF-1α signaling[J].Life Sci, 2015, 136:67-72.
[6] 宋小莉, 苏 娟.PHDs-HIFs-pVHL通路在类风湿关节炎中的研究进展[J].中国现代医学杂志, 2018, 28(6): 59-64.
[6] Song X L, Su J.Systemic rreview on PHDs-HIFs-pVHL pathway in rheumatoid arthritis[J].Chin J Mod Med, 2018, 28(6): 59-64.
[7] Muz B, Larsen H, Madden L, et al.Prolyl hydroxylase domain enzyme 2 is the major player in regulating hypoxic responses in rheumatoid arthritis[J].Arthritis Rheum, 2012, 64(9):2856-67.
[8] Liu S C, Chuang S M, Hsu C J, et al.CTGF increases vascular endothelial growth factor-dependent angiogenesis in human synovial fibroblasts by increasing miR-210 expression[J].Cell Death Dis, 2014, 5:e1485.
[9] 于静雅, 陈 勇.PI3K-AKT信号通路及其在类风湿性关节炎滑膜细胞增殖和凋亡中的作用[J].细胞与分子免疫学杂志, 2014, 30(12): 1326-9.
[9] Yu J Y, Chen Y.PI3K-AKT signaling pathway and its role in proliferation and apoptosis of synovial cells in rheumatoid arthritis[J].Chin J Cell Mol Immunol, 2014, 30(12): 1326-9.
[10] Zou L, Zhang G, Liu L, et al.Relationship between PI3K pathway and angiogenesis in CIA rat synovium[J].Am J Transl Res, 2016, 8(7):3141-7.
[11] 张晓军, 刘 健, 万 磊, 等.基于缺氧诱导因子及PI3K-AKT-mTOR信号通路诱导佐剂关节炎滑膜血管新生的实验观察[J].中国临床保健杂志, 2018, 21(1): 84-7.
[11] Zhang X J, Liu J, Wan L, et al.Experimental observation of PI3K-AKT-mTOR signaling pathway and HIF-1α in synovial angiogenesis rats with adjuvant arthritis[J].Chin J Clin Health, 2018, 21(1): 84-7
[12] Zhang Y, Zhang B.Trichostatin A, an inhibitor of histone deacetylase, inhibits the viability and invasiveness of hypoxic rheumatoid arthritis fibroblast-like synoviocytes via PI3K/Akt signaling[J].J Biochem Mol Toxicol, 2016, 30(4):163-9.
[13] 王建竹, 孔祥英, 林 娜.ERK信号转导通路与类风湿关节炎[J].中国病理生理杂志, 2011, 27(2): 398-402.
[13] Wang J Z, Kong X Y, Lin N.ERK signaling pathway in rheumatoid arthritis[J].Chin J Pathophysiol, 2011, 27(2): 398-402.
[14] Lee J W, Lee J, Um S H, Moon E Y.Synovial cell death is regulated by TNF-α-induced expression of B-cell activating factor through an ERK-dependent increase in hypoxia-inducible factor-1α[J].Cell Death Dis, 2017, 8(4):e2727.
[15] Shen K, Ji L, Gong C, et al.Notoginsenoside Ft1 promotes angiogenesis via HIF-1α mediated VEGF secretion and the regulation of PI3K/AKT and Raf/MEK/ERK signaling pathways[J].Biochem Pharmacol, 2012, 84(6):784-92.
[16] 杨永生, 李荣亨, 董秋梅.JAK/STAT信号通路与类风湿关节炎的相关性探讨[J].风湿病与关节炎, 2018, 7(7): 60-3, 77.
[16] Yang Y S, Li R H, Dong Q M.Correlation between JAK/STAT signaling pathway and rheumatoid arthritis[J].Rheum Arthritis, 2018, 7(7): 60-3, 77.
[17] 甄晓洲, 黄笑妍, 何智映, 等.JAK2/STAT3通路对低氧诱导的THP-1细胞炎症因子表达的影响[J].中国热带医学, 2017, 17(2):118-22.
[17] Zhen X Z, Huang X Y, He Z Y, et al.Effect of JAK2/STAT3 pathway on expression of inflammatory cytokines in hypoxia-induced THP-1 cells[J].Chin Tropical Med, 2017, 17(2): 118-22.
[18] Gao W, McCormick J, Connolly M, et al.Hypoxia and STAT3 signalling interactions regulate pro-inflammatory pathways in rheumatoid arthritis[J].Ann Rheum Dis, 2015, 74(6):1275-83.
[19] 姜申易, 鲁 静.NF-κB在类风湿关节炎中的研究进展[J].中国免疫学杂志, 2016, 32(1): 119-22.
[19] Jiang S Y, Lu J.Research progress of NF-kappa B in rheumatoid arthritis[J].Chin J Immunol, 2016, 32(1): 119-22.
[20] Fearon U, Canavan M, Biniecka M, Veale D J.Hypoxia, mitochondrial dysfunction and synovial invasiveness in rheumatoid arthritis[J].Nat Rev Rheumatol, 2016, 12(7):385-97.
[21] Trebec-Reynolds D P, Voronov I, Heersche J N, Manolson M F.VEGF-A expression in osteoclasts is regulated by NF-kappaB induction of HIF-1alpha[J].J Cell Biochem, 2010, 110(2):343-51.
[22] Park S Y, Lee S W, Kim H Y, et al.HMGB1 induces angiogenesis in rheumatoid arthritis via HIF-1α activation[J].Eur J Immunol, 2015, 45(4):1216-27.
[23] Gao W, Sweeney C, Connolly M, et al.Notch-1 mediates hypoxia-induced angiogenesis in rheumatoid arthritis[J].Arthritis Rheum, 2012, 64(7):2104-13.
[24] 张峥嵘, 吴 虹, 戴 丽, 等.1-磷酸鞘氨醇及受体对自身免疫性疾病血管新生的影响[J].中国药理学通报, 2017, 33(9):1190-4.
[24] Zhang Z R, Wu H, Dai L, et al.Effects of sphingosine-1-phosphate and its receptors on angiogenesis in autoimmune diseases[J].Chin Pharmacol Bull, 2017, 33(9):1190-4.
[25] Sassoli C, Pierucci F, Tani A, et al.Sphingosine 1-phosphate receptor 1 is required for MMP-2 function in bone marrow mesenchymal stromal cells: implications for cytoskeleton assembly and proliferation[J].Stem Cells Int, 2018, 2018:5034679.

相似文献/References:

[1]赵晓辉,岳会兰,梅丽娟,等.塞隆骨提取物对牛Ⅱ型胶原诱导的小鼠关节炎的治疗作用及机制研究[J].中国药理学通报,2008,(03):0.
 ZHAO Xiao hui,YUE Hui lan,MEI Li juan,et al.The effects of Myospalax fontanieri extracts on cattle type Ⅱcollageninduced arthritis[J].Chinese Pharmacological Bulletin,2008,(09):0.
[2]王婷玉,李俊.CD4+CD25+调节性T细胞在类风湿性关节炎中的研究进展[J].中国药理学通报,2008,(11):0.
 WANG Ting yu,LI Jun.Progress of CD4+CD25+ regulatory T cells in rheumatoid arthritis[J].Chinese Pharmacological Bulletin,2008,(09):0.
[3]黄学应,陈飞虎,张晓明,等.内抑素抗血管生成及抗类风湿性关节炎治疗[J].中国药理学通报,2009,(03):0.
 HUANG Xue ying,CHEN Fei hu,ZHANG Xiao ming,et al.Endostatin: antiangiogenic properties and the therapeutic effect on rheumatoid arthritis[J].Chinese Pharmacological Bulletin,2009,(09):0.
[4]张力,万敬员,叶笃筠,等.脂氧素受体激动剂BML111减轻佐剂诱导的关节炎[J].中国药理学通报,2009,(03):0.
 ZHANG Li,WAN Jing yuan,YE Du yun,et al.Lipoxin receptor agonist BML111 alleviates adjuvant arthritis in rats[J].Chinese Pharmacological Bulletin,2009,(09):0.
[5]李霞,袁凤来,赵懿清,等.骨桥蛋白在类风湿性关节炎中的作用[J].中国药理学通报,2012,(02):155.
 LI Xia,YUAN Feng lai,ZHAO Yi qing,et al.Role of osteopontin in rheumatoid arthritis[J].Chinese Pharmacological Bulletin,2012,(09):155.
[6]付静静,张玲玲,魏伟.树突细胞在类风湿性关节炎病理机制中的免疫原性和耐受性双重作用[J].中国药理学通报,2012,(09):1185.
 FU Jing jing,ZHANG Ling ling,WEI Wei.Dual role of dendritic cells in the pathological mechanism of rheumatoid arthritis: immunogenicity and tolerogenicity[J].Chinese Pharmacological Bulletin,2012,(09):1185.
[7]缪成贵,黄成,黄艳,等.Wnt调控类风湿性关节炎研究进展[J].中国药理学通报,2013,(02):149.
 MIAO Cheng gui,HUANG Cheng,HUANG Yan,et al.Research progress of the Wnt in rheumatoid arthritis[J].Chinese Pharmacological Bulletin,2013,(09):149.
[8]杨金娜,刘晓光,李覃,等.Th17/Treg平衡在类风湿关节炎中作用的研究进展[J].中国药理学通报,2013,(08):1045.
 YANG Jin na,LIU Xiao guang,LI Tan,et al.Function of Th17/Treg balance in rheumatoid arthritis[J].Chinese Pharmacological Bulletin,2013,(09):1045.
[9]熊雪婷,许碧莲.Wnt信号通路在类风湿性关节炎发病机制中的研究进展[J].中国药理学通报,2014,(01):13.
 XIONG Xue-ting,XU Bi-lian.Research progress of Wnt signaling pathway in pathogenesis of rheumatoid arthritis[J].Chinese Pharmacological Bulletin,2014,(09):13.
[10]吴青云,熊雪婷,许碧莲,等.泼尼松对Ⅱ型胶原诱导性关节炎大鼠 股骨微结构及生物力学的影响[J].中国药理学通报,2014,(07):1018.
 WU Qing-yun,XIONG Xue-ting,XU Bi-lian,et al.Effects of prednisone on trabecular microstructure and biomechanical properties of femur in a rat model of type II collagen-induced arthritis[J].Chinese Pharmacological Bulletin,2014,(09):1018.

备注/Memo

备注/Memo:
收稿日期:2019-05-20,修回日期:2019-06-24
基金项目:国家自然科学基金面上项目(No 81874360,81473400,81073122); 安徽中医药大学探索性科研项目(No RD17100457); 安徽中医药大学2018级研究生科技创新基金项目
作者简介:孙明慧(1997-),女,硕士生,研究方向:药物作用有效性与活性成分相关性,E-mail:1608273041@qq.com;
吴 虹(1967-),女,博士,教授,博士生导师,研究方向:药物作用有效性与活性成分相关性,通讯作者,E-mail:hongw@aliyun.com
更新日期/Last Update: 2019-08-14