Angiogenic action of gliostatin/thymidine phosphorylase and vascular endothelial growth factor in rheumatoid arthritis and its molecular mechanism

胶质抑素/胸苷磷酸化酶和血管内皮生长因子在类风湿性关节炎中的血管生成作用及其分子机制

• 批准号: 18591670
• 负责人: NAGAYA Yuko
• 金额: $ 2.48万
• 依托单位: Nagoya City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591670/
• 关键词: rheumatoid arthritis; synoviocytes; angogenesis; gliostatin; vascular endnthelial growth factor; DNA microarrav system

Gliostatin/thymidine phosphorylase (GLS/TP) is known to have angiogenic and arthritogenic activities. We previously demonstrated, for the first time, significantly higher concentrations of GLS/TP in the sera and synovial fluids of patients with rheumatoid arthritis (RA) compared to those with osteoarthritis or normal controls. In cultured RA fibroblast-like synoviocytes (FLSs), GLS expression was found to be up-regulated by inflammatory cytokines, such as IL-i and tumour-necrosis factor (TNF)α.The purpose of this study was to elucidate whether GLS/TP is involved in the regulation of the angiogenic cytokine vascular endothelial growth factor (VEGF) in RA. Fibroblast-like synoviocytes (FLSs) from patients with RA were cultured and stimulated with recombinant human GLS (rHuGLS) and interleukin (IL)-1β.Immunohistochemistry showed that GLS/TP and VEGF were detectable in the synovial lining cells from RA patients. GLS/TP and VEGF were even more weakly detected in synovial specimens from osteoarthritis patients than these from RA patients. In cultured FLSs, both VEGF mRNA and protein levels were markedly increased by rHuIL-1β treatment. rHuGLS increased VEGF mRNA expression in a dose-dependent manner. We detected high concentrations of VEGF165 protein in culture supernatants from FLSs treated with rHuGLS (300 ng/ml), which were comparable to GLS levels found in synovial fluid of RA patients. These findings indicate that GLS/TP and VEGF have synergistic effects on angiogenesis in rheumatoid synovitis, and that GLS/TP has a role in regulating VEGF

已知神经胶质素/胸苷磷酸化酶（GLS/TP）具有血管生成和关节炎活性。我们先前首次证明了类风湿关节炎患者（RA）的血清和滑液中的GLS/TP浓度明显更高，与患有骨关节炎或正常对照的患者相比。在培养的RA成纤维细胞样的滑膜细胞（FLS）中，发现GLS表达受炎性细胞因子（例如IL-I和肿瘤 - 脱氧因子（TNF）α）的上调，这项研究的目的是阐明GLS/TP是否参与了囊肿的调节因子的调节，即在调节角色均具有囊性cyantokine Cyfffffffft Inttokine cyfffffft Intoral cyffffffffffft Intoral cyfffffffffffffff。培养了RA患者的成纤维细胞样的滑膜细胞（FLS），并用重组人GL（Rhugls）和白介素（IL）-1β.Mumunoystristry刺激，表明在RA患者的合成细胞中可检测到GLS/TP和VEGF。与RA患者相比，在骨关节炎患者的滑膜标本中，GLS/TP和VEGF的检测到更弱。在培养的FLS中，RhuIL-1β处理显着提高了VEGF mRNA和蛋白质水平。 rhugls以剂量依赖性方式增加了VEGF mRNA的表达。我们检测到来自用Rhugls（300 ng/ml）处理的FLS的培养上清液中的高浓度VEGF165蛋白，这些蛋白与RA患者滑液中的GLS水平相当。这些发现表明，GLS/TP和VEGF对类风湿滑膜炎具有协同作用，并且GLS/TP在调节VEGF中起作用

项目成果

Fate of transplanted nail matrical cells and potential of hard keratin production in vivo.

移植的指甲基质细胞的命运和体内硬角蛋白产生的潜力。

• 发表时间: 2006
• 期刊: J Dermatol Sci 44
• 作者: Okamoto H;et al.
• 通讯作者: et al.

Fate of transplanted nail matrical cells and potential of hard keratin production in vivo

移植的指甲基质细胞的命运和体内硬角蛋白产生的潜力

• 发表时间: 2006
• 期刊: J Dermatol Sci 44
• 作者: Okamoto H;et. al.
• 通讯作者: et. al.

Gliostatin/thymidine phosphorylase-regulated vascular endothelial growth-factor production in human fibroblast-like synoviocytes

胶质抑素/胸苷磷酸化酶调节人成纤维样滑膜细胞中血管内皮生长因子的产生

• 发表时间: 2007
• 期刊: Rheumatol Int 27
• 作者: Tanikawa T;et. al.
• 通讯作者: et. al.

The inhibitory effect of disease-modifying anti-rheumatic drugs and steroids on gliostatin/platelet-derived endothelial cell growth factor production in human fibroblast-like synoviocytes

• DOI: 10.1007/s00296-005-0624-8
• 发表时间: 2005-10-01
• 期刊: RHEUMATOLOGY INTERNATIONAL
• 影响因子: 4
• 作者: Kusabe, T;Waguri-Nagaya, Y;Asai, K
• 通讯作者: Asai, K

Dihydrotestosterone inhibits tumor necrosis factor alpha induced interleukin-1alpha mRNA expression in rheumatoid fibroblast-like synovial cells.

• DOI: 10.1248/bpb.30.1140
• 发表时间: 2007-06
• 期刊: Biological & pharmaceutical bulletin
• 影响因子: 2
• 作者: Yuka Itoh;H. Hayashi;Jian Xu;T. Takii;K. Miyazawa;H. Ariga;T. Akahoshi;Y. Waguri-Nagaya;T. Otsuka;T. Okamoto;K. Onozaki