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

Gliostatin/thymidine磷酸化酶（GLS/TP）具有血管生成和关节炎生成活性。我们之前首次证明，与骨关节炎患者或正常对照相比，类风湿性关节炎（RA）患者血清和滑液中GLS/TP浓度明显更高。在培养的RA成纤维细胞样滑膜细胞（FLSs）中，发现炎性细胞因子如il - 1和肿瘤坏死因子(TNF)α上调GLS表达。本研究的目的是阐明GLS/TP是否参与RA血管生成细胞因子血管内皮生长因子（VEGF）的调控。用重组人GLS （rHuGLS）和白细胞介素(IL)-1β刺激RA患者成纤维细胞样滑膜细胞（FLSs）。免疫组化结果显示，RA患者滑膜衬里细胞中可检测到GLS/TP和VEGF。GLS/TP和VEGF在骨关节炎患者的滑膜标本中比在RA患者的滑膜标本中更弱。在培养的FLSs中，rHuIL-1β处理后VEGF mRNA和蛋白水平均显著升高。rHuGLS呈剂量依赖性增加VEGF mRNA表达。我们在用rHuGLS （300 ng/ml）处理的fls培养上清液中检测到高浓度的VEGF165蛋白，其水平与RA患者滑液中的GLS水平相当。这些结果提示GLS/TP与VEGF在类风湿滑膜炎血管生成中具有协同作用，GLS/TP具有调节VEGF的作用

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.

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

二氢睾酮抑制类风湿成纤维样滑膜细胞中肿瘤坏死因子 α 诱导的白细胞介素-lα mRNA 表达。

• 发表时间: 2007
• 期刊: Biol. Pharm. Bull
• 作者: Itoh;T.
• 通讯作者: T.

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.

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