Characterization of osteoprotegerin-induced signaling in human endothelial cells

人内皮细胞中骨保护素诱导的信号传导的表征

• 批准号: 22592097
• 负责人: KOBAYASHI Michiyo
• 金额: $ 2.33万
• 依托单位: Hokkaido University (2011-2012)Health Sciences University of Hokkaido (2010)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22592097/
• 关键词: 免疫; 感染; 炎症; オステオプロテゲリン; 炎症性サイトカイン; トロンビン; 血管内皮細胞

Background and Objectives: Thrombin is a procoagulant and proinflammatory molecule that is also a potential mediator of bone resorption . Osteoprotegerin (OPG) is a key molecule that binds to the receptor-activator of the nuclear factor-κB (NF-κB) ligand (RANKL), and inhibits osteoclast differentiation. This study aimed to evaluate the biological effects of thrombin on OPG production in human dermal microvascular endothelial cells (HMVEC). Materials and Methods: HMVEC were treated with 2.1-11.2 U/mL of thrombin for 18 h. Thrombin-induced OPG production was assessed by enzyme-linked immunosorbent assay (ELISA). Inhibitors were used to investigate the influence of thrombin on OPG production in HMVEC and the thrombin-signaling pathway. Results: Thrombin induced OPG production in HMVEC in a dose-dependent manner. The phosphatidylinositol 3-kinase (PI3K) inhibitor and Src kinase inhibitor exerted an inhibitory effect on thrombin-induced OPG expression. Thrombin-induced OPG production was also inhibited by the protease-activated receptor (PAR)-1 antagonist. Conclusion: Thrombin induces OPG expression in HMVEC, possibly through PAR-1. Thrombin-induced OPG production is regulated by the PI3K and Src pathways. These findings suggest that thrombin may play a significant role in regulating the levels of serum OPG.

背景和目的：凝血酶是一种促凝剂和促炎分子，也是骨吸收的潜在介质。骨保护素（Osteoprotegerin， OPG）是与核因子-κB （NF-κB）配体受体激活因子（receptor-activator of nuclear factor-κB， RANKL）结合，抑制破骨细胞分化的关键分子。本研究旨在评价凝血酶对人皮肤微血管内皮细胞（HMVEC） OPG生成的生物学效应。材料与方法：以2.1 ~ 11.2 U/mL凝血酶处理HMVEC 18 h，采用酶联免疫吸附试验（ELISA）检测凝血酶诱导OPG的产生。利用抑制剂研究凝血酶对HMVEC中OPG生成和凝血酶信号通路的影响。结果：凝血酶诱导HMVEC产生OPG呈剂量依赖性。磷脂酰肌醇3-激酶（PI3K）抑制剂和Src激酶抑制剂对凝血酶诱导的OPG表达有抑制作用。凝血酶诱导的OPG生成也被蛋白酶激活受体(PAR)-1拮抗剂抑制。结论：凝血酶可能通过PAR-1诱导了OPG在HMVEC中的表达。凝血酶诱导的OPG的产生受PI3K和Src途径的调控。这些发现提示凝血酶可能在调节血清OPG水平中起重要作用。

项目成果

inhibition of angiogenesis and cell proliferation by royal jelly

蜂王浆抑制血管生成和细胞增殖

• 发表时间: 2010
• 作者: Takayuki Tsukuba;Michiyo Yanagawa;Tomoko Kadowaki;Yoshiko Okamoto;Kuniaki Okamoto;Kenji Yamamoto;Daiji Kobayashi
• 通讯作者: Daiji Kobayashi

Anti-glucosyltransferase IgY suppresses salivary mutans streptococci in volunteers

抗葡萄糖基转移酶 IgY 抑制志愿者唾液变形链球菌

• 发表时间: 2011
• 期刊: The Journal of the American Dental Association
• 作者: Nguyen SV.;Icatlo FC Jr.;Nakano T.;Isogai E;Hirose K.;Mizugai H.;Kobayashi- SakamotoM .;IsgaiH ;ChibaI
• 通讯作者: ChibaI

血管内皮細胞におけるオステオプロテゲリンの役割とその作用機序の解明

阐明骨保护素对血管内皮细胞的作用及其作用机制

• 发表时间: 2010
• 作者: 杜媛;橋爪智美;落合智子;安孫子宜光;山本正文;西下一久,坂井詠子,岡元邦彰,筑波隆幸;杉本是明;小林美智代,磯貝恵美子,広瀬公治
• 通讯作者: 小林美智代,磯貝恵美子,広瀬公治

Osteoprotegerin induces cytoskeletal reorganization and activates FAK, Src, and ERK signaling in endothelial cells

• DOI: 10.1111/j.1600-0609.2010.01446.x
• 发表时间: 2010-07-01
• 期刊: EUROPEAN JOURNAL OF HAEMATOLOGY
• 影响因子: 3.1
• 作者: Kobayashi-Sakamoto, Michiyo;Isogai, Emiko;Holen, Ingunn
• 通讯作者: Holen, Ingunn

マダニデフェンシンの中腸由来細菌に対する抗菌活性

蜱防御素对中肠来源细菌的抗菌活性

• 发表时间: 2011
• 期刊: 無菌生物
• 作者: 磯貝恵美子;秋葉敬斎;岡 翔太;堀 初弘;磯貝 浩;小林美智代;奥村一彦
• 通讯作者: 奥村一彦