KIAA1199 as a potential diagnostic biomarker of rheumatoid arthritis related to angiogenesis.
KIAA1199 as a potential diagnostic biomarker of rheumatoid arthritis related to angiogenesis.
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KIAA1199 作为与血管生成相关的类风湿性关节炎的潜在诊断生物标志物
DOI：
10.1186/s13075-015-0637-y
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发表时间：
2015-05-29
影响因子：
4.9
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Yang X;Qiu P;Chen B;Lin Y;Zhou Z;Ge R;Zou H;Wang J;Wang J
我们对滑膜组织中的成纤维细胞样滑膜细胞（FLS）进行了蛋白质组学研究，发现KIAA 1199在类风湿关节炎（RA）患者中的表达高于健康对照。本研究旨在探讨KIAA 1199的生物学功能，并评价其在RA中的临床诊断价值。方法采用实时定量聚合酶链反应（qPCR）、免疫组织化学、免疫荧光和酶联免疫吸附试验（ELISA）等方法，验证KIAA 1199在活动期、非活动期RA患者和健康对照中的过表达。通过MTT法、细胞迁移、小管形成、绒毛尿囊膜（CAM）实验、qPCR和Western-blotting等方法分析KIAA 1199基因敲低和过表达后对FLS增殖、血管生成及相关通路的影响。ELISA和受试者工作特征（ROC）分析表明，血清、滑液和滑膜组织中KIAA 1199浓度可作为诊断活动性RA的可靠生物标志物，ROC曲线下面积（AUC）分别为0.83、0.92和0.92。以临界值确定的敏感性和特异性分别为72%、84%和80%，特异性分别为80%、93.3%和93.3%。此外，KIAA 1199还增强滑膜的增殖和血管生成，KIAA 1199/PLXNB 3/SEMA 5A/CTGF轴可能是新发现的增强细胞增殖和血管生成的途径。结论KIAA 1199可能是与血管生成相关的RA潜在诊断生物标志物。
IntroductionOur previous proteomic study on fibroblast-like synoviocytes (FLSs) derived from the synovial tissues found that the expression of KIAA1199 was higher in rheumatoid arthritis (RA) patients than in healthy controls. The aim of this study was to examine the biological function of KIAA1199 and evaluate its clinical diagnosis value in RA.MethodsThe over-expression of KIAA1199 was verified by quantitative real-time polymerase chain reaction (qPCR), Immunohistochemistry, Immunofluorescence and enzyme linked immunosorbent assay (ELISA) in inactive and active RA patients and healthy controls. The effect of KIAA1199 expression on FLSs proliferation, angiogenesis and related pathway were analyzed by MTT, cell migration, tube formation, chorioallantoic membrane (CAM) assay, qPCR and western-blotting after KIAA1199 knockdown and over-expression.ResultsThe verification results show the up-regulation of KIAA1199 in RA patients at mRNA and protein level as compared to that in healthy controls. ELISA and receiver operator characteristic (ROC) analysis shows that KIAA1199 concentration in serum, synovial fluid and synovial tissues could be used as dependable biomarkers for the diagnosis of active RA, provided an area under roc curve (AUC) of 0.83, 0.92 and 0.92. Sensitivity and specificity, which were determined by cut-off points, reached 72% 84% and 80% in sensitivity and 80%, 93.3%, 93.3% in specificity, respectively. Moreover, KIAA1199 also enhance the proliferation and angiogenesis of synovial membrane, and KIAA1199/ PLXNB3/ SEMA5A/CTGF axis may be a newly found pathway enhancing cell proliferation and angiogenesis.ConclusionKIAA1199 may be a potential diagnostic biomarker of RA related to angiogenesis.
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影响因子：
15.9
作者：
Lin, Ling;Lesnick, Timothy G.;Maraganore, Demetrius M.;Isacson, Ole
通讯作者：
Isacson, Ole
影响因子：
5.3
作者：
Fiore, R;Rahim, B;Püschell, AW
通讯作者：
Püschell, AW
影响因子：
3.7
作者：
Matsuzaki, Shinji;Tanaka, Fumiaki;Mori, Masaki
通讯作者：
Mori, Masaki
影响因子：
5.8
作者：
He, Quan-Yuan;Liu, Xiang-Hua;Liang, Song-Ping
通讯作者：
Liang, Song-Ping
DOI：
10.1083/jcb.114.6.1285
发表时间：
1991-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bradham DM;Igarashi A;Potter RL;Grotendorst GR
通讯作者：
Grotendorst GR