Role of coagulation factor 3 in diabetic nephropathy

凝血因子3在糖尿病肾病中的作用

• 批准号: 22890016
• 负责人: TAKAHASHI Nobuyuki
• 金额: $ 2.01万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Research Activity Start-up
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-22890016/
• 关键词: 糖尿病性腎症; 凝固第三因子; マウス; 血液凝固; 一酸化窒素合成酵素; 内皮型一酸化窒素合成酵素; 凝固第3因子; アキタマウス; マクロファージ

Diabetic nephropathy (DN)is the leading cause of end stage renal disease, and the number of patients with DN has been increasing rapidly. Human variants of the endothelial nitric oxide synthase gene (eNOS, NOS3)that produce reduced amounts of nitric oxide (NO)are positively associated with DN, although proof of causation is lacking. Here we have demonstrated that eNOS-/-mice with diabetes develop severe nephropathy. However, complete absence of eNOS has not been reported in humans, although reduced levels are not infrequent. Accordingly, heterozygous eNOS+/-mice have been made diabetic, and they demonstrated that the decrease in eNOS/NO comparable to that of NOS3 polymorphisms is sufficient to cause exacerbation of DN. Increased expression of tissue factor, initiator of coagulation, likely plays a significant role in the DN of the eNOS-/-diabetic mice. Strategies to ameliorate hypercoagulability could be useful for treatment of DN.

糖尿病肾病（Diabetic nephropathy， DN）是终末期肾脏疾病的主要病因，且患者数量呈快速增长趋势。内皮型一氧化氮合酶基因（eNOS, NOS3）的人类变体产生减少的一氧化氮（NO）与DN呈正相关，尽管缺乏因果关系的证据。在这里，我们已经证明患有糖尿病的eNOS-/-小鼠会发生严重的肾病。然而，尽管eNOS水平降低的情况并不少见，但人类中eNOS的完全缺失尚未见报道。因此，杂合的eNOS+/-小鼠被制造为糖尿病，他们证明eNOS/NO的减少与NOS3多态性的减少相当，足以导致DN的恶化。凝血引发剂组织因子的表达增加可能在eNOS-/-糖尿病小鼠的DN中起重要作用。改善高凝性的策略可能有助于DN的治疗。

项目成果

糖尿病性腎症におけるeNOS・NO減少と高脂肪食の役割

eNOS/NO 减少和高脂饮食在糖尿病肾病中的作用

• 发表时间: 2012
• 作者: 高橋信行、Feng Li;Chih-Hong Wang;Nigel Mackman;Nobuyo Maeda;Oliver Smithies;J Charles Jennette;佐藤博、伊藤貞嘉
• 通讯作者: 佐藤博、伊藤貞嘉

A modest decrease in endothelial NOS in mice comparable to that associated with human NOS3 variants exacerbates diabetic nephropathy.

与人类 NOS3 变异相关的小鼠内皮 NOS 的适度减少会加剧糖尿病肾病。

• DOI: 10.1073/pnas.1018766108
• 发表时间: 2011
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: Wang,Chih-Hong;Li,Feng;Hiller,Sylvia;Kim,Hyung-Suk;Maeda,Nobuyo;Smithies,Oliver;Takahashi,Nobuyuki
• 通讯作者: Takahashi,Nobuyuki

ENOS and diabetic nephropathy

ENOS 与糖尿病肾病

• 发表时间: 2015
• 作者: Nozu T;Miyagishi S;Nozu R;Takakusaki K;Okumura T.;Takahiko Nakagawa
• 通讯作者: Takahiko Nakagawa