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山东大学学报（医学版） ›› 2017, Vol. 55 ›› Issue (3): 88-93.doi: 10.6040/j.issn.1671-7554.0.2016.929

• 临床医学 • 上一篇    下一篇

筛选TXNDC5与胰岛素相关信号通路关键基因的探讨

李健1,2,徐冰2,闫新峰3,徐万菊4,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医学研究中心, 山东 济南 250014;3. 山东大学附属千佛山医院骨科, 山东 济南 250014;4.山东大学附属千佛山医院检验科, 山东 济南 250014
  • 收稿日期:2016-08-01 出版日期:2017-03-10 发布日期:2017-03-10
  • 通讯作者: 常晓天. E-mail:chang-xt@163.com E-mail:chang-xt@163.com
  • 基金资助:
    山东省自然科学基金(ZR2014HP018);山东省医药卫生科技发展计划(2013WS0131)

Screening key genes for TXNDC5 and insulin signaling pathway

LI Jian1,2, XU Bing2, YAN Xinfeng3, XU Wanju4, CHANG Xiaotian2   

  1. 1. School of Medicine, Shandong University, Jinan 250012, Shandong, China;
    2. Medical Research Center;
    3. Department of Orthopedics;
    4. Clinical Laboratory, Qianfoshan Hospital, Shandong University, Jinan 250014, Shandong, China
  • Received:2016-08-01 Online:2017-03-10 Published:2017-03-10

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摘要： 目的 旨在探讨硫氧还蛋白5(TXNDC5)是否通过胰岛素抵抗或胰岛素信号通路参与类风湿关节炎(RA)发病过程。 方法 分离培养RA滑膜细胞(RASFs),用小干扰RNA抑制其TXNDC5的表达,提取各样本总RNA组成样本池,采用胰岛素抵抗PCR Array和胰岛素信号通路PCR Array检测相关基因的表达,采用RT-PCR法和ELISA法分别检测相关基因mRNA和蛋白水平的表达。 结果 RASFs中TXNDC5表达被抑制后, PCR Array检测IGF-1、 PCK1、 SLC2A4、IL1R1和胰岛素样生长因子结合蛋白1(IGFBP1)的表达明显发生变化。经验证,IGFBP1在mRNA和蛋白水平均显著增高,差异有统计学意义(P均<0.001);而IGF-1、PCK1、SLC2A4和IL1R1的表达差异无统计学意义(P=0.792 7,P=0.713 0,P=0.452 9,P=0.354 2)。胰岛素样生长因子结合蛋白3(IGFBP3)在RASFs中的表达无明显变化(P=0.511 5)。 结论 在RASFs中,TXNDC5可能通过抑制胰岛素信号通路IGFBP1表达参与RA病变过程。

关键词: 类风湿关节炎, 胰岛素抵抗, 硫氧还蛋白5, 胰岛素样生长因子结合蛋白1, 胰岛素信号通路

Abstract: Objective To explore the pathogenic mechanism of thioredoxin domain containing protein 5(TXNDC5)involvement in rheumatoid arthritis(RA). Methods Human rheumatoid arthritis synovial cells(RASFs)were separated from RA patients. After the TXNDC5 expression was inhibited by anti-TXNDC5 siRNA, the total RNA was pooled, and the expressions of related genes were detected with PCR Array. The mRNA and protein expressions of related genes were verified using RT-PCR and ELISA. Results PCR Array analyses demonstrated that IGF-1, PCK1, SLC2A4, IL1R and IGFBP1 expressions significantly changed after TXNDC5 expression was inhibited. RT-PCR and ELISA verification indicated that IGFBP1 expression was significantly enhanced in both mRNA and protein levels(both P<0.001), while expressions of IGF-1, PCK1, SLC2A4 and IL1R1 showed no significant difference(P=0.792 7, P=0.713 0, P=0.452 9, P=0.354 2). No difference was observed in IGFBP3 expressions(P=0.511 5). Conclusion In RASFs, TXNDC5 is involved in RA by regulating the expression of IGFBP1.

Key words: Insulin-like growth factor binding protein 1, Rheumatoid arthritis, Thioredoxin domain containing protein 5, Insulin resistance, Insulin signal pathway

中图分类号: 

  • R34
[1] Knoblach B, Keller BO, Groenendyk J, et al. ERp19 and ERp46, new members of the thioredoxin family of endoplasmic reticulum proteins[J]. Mol Cell Proteomics, 2003, 2(10):1104-1119.
[2] Freedman RB, Hirst TR, Tuite MF. Protein disulphide isomerase: building bridges in protein folding [J]. Trends Biochem Sci, 1994, 19(8):331-336.
[3] 赵琰, 郑亚冰, 闫新峰, 等. 筛选类风湿关节炎中糖代谢关键基因的探讨[J]. 山东大学学报(医学版), 2016, 54(3):1-7. ZHAO Yan, ZHENG Yabing, YAN Xingfeng, et al. Screening crucial genes for glucose metabolism in rheumatoid arthritis [J]. Journal of Shandong University(Health Sciences), 2016, 54(3):1-7.
[4] 舒强, 李兴福, 刘花香, 等. 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. SHU Qiang, LI Xingfu, LIU Huaxiang, et al. Proliferation of fibroblast-like synovial cells in patients with rheumatoid arthritis in vitro[J]. Journal of Shandong University(Health Sciences), 2006, 44(11):1095-1099.
[5] Chang X, Cui Y, Zong M, et al. Identification of proteins with increased expression in rheumatoid arthritis synovial tissues[J]. J Rheumatol, 2009, 36(5):872-880.
[6] Wang L, Zheng Y, Xu H, et al. Investigate pathogenic mechanism of TXNDC5 in rheumatoid arthritis[J]. PLoS One, 2013, 8(1):53301.
[7] Wolf AM, Wolf D, Rumpold H, et al. Adiponectin induces the anti-inflammatory cytokines IL-10 and IL-1RA in human leukocytes[J]. Biochem Biophys Res Commun, 2004, 323(2):630-635.
[8] Senolt L, Pavelka K, Housa D, et al. Increased adiponectin is negatively linked to the local inflammatory process in patients with rheumatoid arthritis[J]. Cytokine, 2006, 35(5-6):247-252.
[9] Liao KP, Solomon DH. Traditional cardiovascular risk factors, inflammation and cardiovascular risk in rheumatoid arthritis[J]. Rheumatology(Oxford), 2013, 52(1): 45-52.
[10] AbouAssi H, Tune KN, Gilmore B, et al. Adipose depots, not disease-related factors, account for skeletal muscle insulin sensitivity in established and treated rheumatoid arthritis[J]. J Rheumatol, 2014, 41(10):1974-1979.
[11] Suzuki S, Morimoto S, Fujishiro M, et al. Inhibition of the insulin-like growth factor system is a potential therapy for rheumatoid arthritis[J]. Autoimmunity, 2015, 48(4): 251-258.
[12] Li AH, Morrison AC, Kovar C, et al. Analysis of loss-of-function variants and 20 risk factor phenotypes in 8,554 individuals identifies loci influencing chronic disease[J]. Nat Genet, 2015, 47(6):640-642.
[13] Holmgren A. Thioredoxin catalyzes the reduction of insulin disulfides by dithiothreitol and dihydrolipoamide[J]. J Bioi Chem, 1979, 254(19):9627-9632.
[17] Jones JI, Clemmons DR. Insulin-like growth factors and their binding proteins: biological actions[J]. Endocr Rev, 1995, 16(1):3-34.
[15] Mezi S, Todi L, Orsi E, et al. Involvement of the Src-cortactin pathway in migration induced by IGF-1 and EGF in human breast cancer cells[J]. Int J Oncol, 2012, 41(6):2128-2138.
[16] Terry KL, Tworoger SS, Gates MA, et al. Common genetic variation in IGF1, IGFBP1 and IGFBP3 and ovarian cancer risk[J]. Carcinogenesis, 2009, 30(12):2042-2046.
[17] Zhu S, Xu F, Zhang J, et al. Insulin-like growth factor binding protein-related protein 1 and cancer[J]. Clin Chim Acta, 2014, 431:23-32.
[18] Unterman T, Lascon R, Gotway MB, et al. Circulating levels of insulin-like growth factor binding protein-1(IGFBP-1)and hepatic mRNA are increased in the small for gestational age(SGA)fetal rat[J]. Endocrinology, 1990, 127(4):2035-2037.
[19] Ben LN, Menuelle P, Seurin D, et al. Bone formation in the context of growth retardation induced by hIGFBP-1 overexpression in transgenic mice[J]. Connect Tissue Res, 2002, 43(2-3):515-519.
[20] Tamura K, Hashimoto K, Suzuki K, et al. Insulin-like growth factor binding protein-7(IGFBP7)blocks vascular endothelial cell growth factor(VEGF)-induced angiogenesis in human vascular endothelial cells[J]. Eur J Pharmacol, 2009, 610(1-3):61-67.
[21] Keyszer GM, Heer AH, Kriegsmann J, et al. Detection of insulin-like growth factor I and II in synovial tissue specimens of patients with rheumatoid arthritis and osteoarthritis by in situ hybridization[J]. J Rheumatol, 1995, 22(2):275-281.
[22] Chang X, Zhao Y, Yan XF, et al. Investigating a pathogenic role for TXNDC5 in rheumatoid arthritis[J]. Arthritis Res Ther, 2011, 13(4):R124.
[23] Heald AH, Cruickshank JK, Riste LK, et al. Close relation of fasting insulin-like growth factor binding protein-1(IGFBP-1)with glucose tolerance and cardiovascular risk in two populations[J]. Diabetologia, 2001, 44(3):333-339.
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