您的位置:山东大学 -> 科技期刊社 -> 《山东大学学报(医学版)》

山东大学学报(医学版) ›› 2016, Vol. 54 ›› Issue (3): 30-35.doi: 10.6040/j.issn.1671-7554.0.2015.842

• • 上一篇    下一篇

筛选类风湿关节炎中糖代谢关键基因的探讨

赵琰1,2,郑亚冰2,闫新峰3,张虎3,常晓天2   

  1. 1. 山东大学医学院, 山东 济南 250012;2. 山东大学附属千佛山医院中心实验室, 山东 济南 250014;3. 山东大学附属千佛山医院骨科, 山东 济南 250014
  • 收稿日期:2015-09-06 出版日期:2016-03-10 发布日期:2016-03-10
  • 通讯作者: 常晓天. E-mail:chang-xt@163.com E-mail:chang-xt@163.com

Screening crucial genes for glucose metabolism in rheumatoid arthritis

ZHAO Yan1,2, ZHENG Yabing2, YAN Xinfeng3, ZHANG Hu3, CHANG Xiaotian2   

  1. 1. School of Medicine, Shandong University, Jinan 250012, Shandong, China;
    2. Medical Research Center, Qianfoshan Hospital, Shandong University, Jinan 250014, Shandong, China;
    3. Department of Orthopedics, Qianfoshan Hospital, Shandong University, Jinan 250014, Shandong, China
  • Received:2015-09-06 Online:2016-03-10 Published:2016-03-10

摘要: 目的 探讨糖代谢关键酶在类风湿关节炎(RA)中的表达,进一步探讨糖代谢与RA的相关性。 方法 取牛Ⅱ型胶原诱导大鼠(CIA组)和正常大鼠(NCR组)膝关节滑膜组织,提取总RNA,采用Rat Glucose Metabolism RT2 ProfilerTM PCR Array筛选表达不一致基因;采用RT-PCR法对CIA组和NCR组进行mRNA水平的检测,采用RT-PCR法和Western blotting法检测RA组和骨关节炎组(OA组)滑膜组织中基因mRNA水平和蛋白水平的表达。收集RA血清(RAB组)和正常献血者血清(NCB组),采用ELISA法检测血清中的表达水平。 结果 PCR Array检测显示,CIA组烯醇化酶(ENO1)、己糖激酶2(HK2)、磷酸甘油酸激酶-1(PGK1)较NCR组表达上调(P<0.05),磷酸烯醇式丙酮酸羧激酶-1(PCK1)和丙酮酸脱氢酶激酶-4(PDK4)表达下调(P<0.05); RT-PCR法和Western blotting法检测显示,RA组与OA组相比, ENO1和PGK1表达上调(P<0.05),ELISA法检测结果显示,RAB组与NCB组相比,PGK1表达升高(P<0.05)。 结论 牛Ⅱ型胶原诱导大鼠和RA滑膜组织中糖代谢关键酶ENO1和PGK1表达增高,RA血液中PGK1表达增加,均提示RA中糖代谢活动增强,导致相关基因的表达异常。

关键词: 类风湿关节炎, 磷酸甘油酸酯激1, 葡萄糖代谢, 胶原诱导型关节炎, 烯醇化酶α

Abstract: Objective To determine the crucial enzymes of glucose metabolism in rheumatoid arthritis(RA). Methods The glucose metabolism in synovial tissues of collagen-induced arthritis(CIA)was analyzed with Rat Glucose Metabolism RT2 ProfilerTM PCR Array. The result was verified using real time PCR, Western blotting and ELISA in synovial tissues and blood from patients with RA. Results The PCR array detected up-regulation of ENO1, HK2 and PGK1, and down-regulation of PCK1 and PDK4 in synovial tissues of CIA rats. Real time PCR and Western blotting detected increased expressions of ENO1 and PGK1 in synovial tissues of RA. ELISA detected a high level of PGK1 in blood of RA patients. The result identified the increased expression of ENO1 and PGK1 in CIA and RA synovial tissues, and elevated level of PGK1 in blood of the patients with RA. Conclusion Glycolytic activity is increased in RA, which may result in the abnormal expression of genes involved.

Key words: Rheumatoid arthritis, Collagen-inducing arthritis, Enolase1(alpha), Glucosemetabolism, Phosphoglycerate kinase 1

中图分类号: 

  • R593.22
[1] Henderson B, Bitensky L, Johnstone JJ. Glycolytic activity in human synovial lining cells in rheumatoid arthritis[J]. Ann Rheum Dis, 1979, 38(5):463-466.
[2] Ciurtin C, Cojocaru VM, Miron IM. Correlation between different components of synovial fluid and pathogenesis of rheumatic diseases[J]. Rom J Intern Med, 2006, 44(2):171-181.
[3] Naughton D, Whelan M, Smith EC, et al. An investigation of the abnormal metabolic status of synovial fluid from patients with rheumatoid arthritis by high field proton nuclear magnetic resonance spectroscopy[J]. FEBS Lett, 1993, 317(1-2):135-138.
[4] Tak PP, Zvaifler NJ, Green DR, et al. Rheuatoid arthritis and p53:how oxidative stress might alter the course of inflammatory diseases[J]. Immunol Today, 2000, 21(2):78-82.
[5] Chang X, Cui Y, Zong M, et al. Identification of proteins with increased expression in synovial tissues of rheumatoid arthritis[J]. J Rheumatol, 2009, 36(5):872-880.
[6] Chang X, Wei C. Glycolysis and Rheumatoid Arthritis[J]. Int J Rheum Dis, 2011, 14(3):217-222.
[7] Hitchon CA, El-Gabalawy HS, Bezabeh T. Characterization of synovial tissue from arthritis patients:a proton magnetic resonance spectroscopic investigation[J]. Rheumatol Int, 2009, 29(10):1205-1211.
[8] Szekanecz Z, Besenyei T, Paragh G, et al. New insights in synovial angiogenesis[J]. Joint Bone Spine, 2010, 7(1):13-19.
[9] Lardner A. The effects of extracellular pH on immune function[J]. J Leukoc Biol, 2001, 69(4):522-530.
[10] Tomura H, Mogi C, Sato K, et al. Proton-sensing and lysolipid sensitive G-protein-coupled receptors:a novel type of multi-functional receptors[J]. Cell Signal, 2005, 17(12):1466-1476.
[11] Ward TT, Steigbigel RT. Acidosis of synovial fluid correlates with synovial fluid leukocytosis[J]. Am J Med, 1978, 64(6):933-936.
[12] Farr M, Garvey K, Bold M, et al. Significance of the hydrogen ion concentration in synovial fluid in rheumatoid arthritis[J]. Clin Exp Rheumatol, 1985, 3(2):99-104.
[13] Muz B, Khan MN, Kiriakidis S, et al. The role of hypoxia and HIF-dependents signaling events in rheumatoid arthritis[J]. Res Ther, 2009, 11(1):201.
[14] Montes A, Dieguez-Gonzalez R, Perez-Pampin E, et al, Particular association of clinical and genetic features with autoimmunity to citrullinated α-enolase in rheumatoid arthritis[J]. Arthritis Rheum, 2011, 63(3):654-661.
[15] Go(¨overe)b V, Thomas-L'Otellier M, Daveau R, et al. Candidate autoantigens identified by mass spectrometry in early rheumatoid arthritis are chaperones and citrullinated glycolytic enzymes[J]. Arthritis Res Ther, 2009, 11(2):38.
[16] Wang TY, Zhou H, Wong YF, et al. The Predicted Proteomic Network Associated with the Antiarthritic Action of QingfuGuanjieshu in Collagen-II-Induced Arthritis in Rats[J]. Evid Based Complement Alternat Med, 2013, 77(1):13-19.
[17] Ahmad SS, Glatzle J, Bajaeifer K, et al. Phosphoglycerate kinase 1 as a promoter of metastasis in colon cancer[J]. Int J Oncol, 2013, 43(2):586-590.
[18] Zieker D, K(¨overo)nigsrainer I, Weinreich J, et al. Phosphoglycerate kinase 1 promoting tumor progression and metastasis in gastric cancer-detected in a tumor mouse model using positron emission tomography/magnetic resonance imaging[J]. Cell Physiol Biochem, 2010, 26(2):147-154.
[19] Zieker D, K(¨overo)nigsrainer I, Traub F, et al. PGK1 a potential marker for peritoneal dissemination in gastric cancer[J]. Cell Physiol Biochem, 2008, 21(5-6):429-436.
[20] Wang J, Wang J, Dai J, et al. A glycolytic mechanism regulating an angiogenic switch in prostate cancer[J]. Cancer Res, 2007, 67(1):149-159.
[21] Szekanecz Z, Besenyei T, Paragh G, et al. New insights in synovial angiogenesis[J]. Joint Bone Spine, 2010, 77(1):13-19.
[22] Verma M, Dutta SK. DNA sequence sencodingenolase are remarkably conserved from yeast to mammals[J]. Life Sci, 1994, 55(12):893-899.
[23] Saulot V, Vittecoq O, Charlionet R, et al. Presence of autoantibodies to the glycolytic enzyme α-enolase in sera from patients with early rheumatoid arthritis[J]. Arthritis Rheum, 2002, 46(5):1196-1201.
[24] Montes A, Perez-Pampin E, Calaza M, et al. Association of anti-citrullinatedvimentin and anti-citrullinated α-enolase with subsets of rheumatoid arthritis[J]. Arthritis Rheum, 2012, 64(10):3102-3110.
[25] Bae S, Kim H, Lee N, et al. α-Enolase expressed on the surfaces of monocytes and macrophages induces robust synovial inflammation in rheumatoid arthritis[J]. J Immunol, 2012, 189(1):365-372.
[26] Hollander AP, Corke KP, Freemont AJ, et al. Expression of hypoxia inducible factor 1 alpha by macrophages in the rheumatoid synovium: implications for targeting of the rapeutic gene to the inflamed joint[J]. Arthritis Rheum, 2001, 44(7):1540-1544.
[27] Giatromanolaki A, Sivridis E, Maltezos E, et al. Upregulated hypoxia inducible factor-1 alpha and-2 alpha pathway in rheumatoid arthritis and osteoarthritis[J]. Arthritis Res Ther, 2003, 5(4):193-201.
[28] Mobasheri A, Richardson S, Mobasheri R, et al. Hypoxia inducible factor-1 and facilitative glucose transporters GLUT1 and GLUT3:putative molecular components of the oxygen and glucose sensing apparatus in articular chondrocytes[J]. Histol Histopathol, 2005, 20(4):1327-1338.
[29] 常晓天, 赵燕. 类风湿关节炎蛋白质组学的研究进展[J]. 医学综述, 2009, 15(20):23-25. CHANG Xiaotian, ZHAO Yan. Progress in rheumatoid arthritis proteomics research[J]. Medical Recapitulate, 2009, 15(20):23-25.
[30] 刘元刚, 刘树滔, 饶平凡. 类风湿性关节炎啮齿动物模型的研究进展[J]. 中国实验动物学报, 2007, 15(6):470-473. LIU Yuangang, LIU Shutao, RAO Pingfan. Recent advances in research on rodent models of rheumatoid arthritis[J]. Acta Lab Anim Sci Sin, 2007, 15(6):470-473.
[1] 李健,徐冰,闫新峰,徐万菊,常晓天. 筛选TXNDC5与胰岛素相关信号通路关键基因的探讨[J]. 山东大学学报(医学版), 2017, 55(3): 88-93.
[2] 姜慧钰, 王林, 潘继红. siRNA沉默PCSK6基因对胶原诱导性关节炎的影响[J]. 山东大学学报(医学版), 2015, 53(12): 20-26.
[3] 郑加田,朱凯,孙红胜,付敏,潘正论. IL-18和MCP-1基因多态性与类风湿关节炎易感性关系的Meta分析[J]. 山东大学学报(医学版), 2014, 52(6): 98-104.
[4] 庄泳, 李栋, 付金秋, 时庆, 鞠秀丽. 儿童B系急性淋巴细胞白血病树突状细胞的生物学特性[J]. 山东大学学报(医学版), 2014, 52(11): 60-64.
[5] 李凤1,许菁2,郑加田1,张源潮1,孙红胜1,潘正论1. 山东地区汉族人群类风湿关节炎与CD14基因多态性的关联性[J]. 山东大学学报(医学版), 2013, 51(4): 87-91.
[6] 张玉军,丁峰,王春晓,李兴福,遇晓. 99Tc-MDP对大鼠佐剂性关节炎PGE1和PGE2的影响[J]. 山东大学学报(医学版), 2010, 48(8): 50-53.
[7] 韦超1,吴围屏1,赵燕1,王林1,闫新峰2 ,常晓天1. 雌激素对胶原诱导关节炎动物模型发病过程的作用[J]. 山东大学学报(医学版), 2010, 48(8): 54-59.
[8] 葛勇鹏,杨清锐,张源潮. 类风湿关节炎与肿瘤坏死因子受体Ⅱ196位点多态性相关性的Meta分析[J]. 山东大学学报(医学版), 2010, 48(5): 79-84.
[9] 舒强,李栋,李兴福,刘花香 . 类风湿关节炎滑膜成纤维样细胞增殖特性的体外研究[J]. 山东大学学报(医学版), 2006, 44(11): 1095-1099.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!