The effect of advanced glycation end-products on blood-nerve barrier

晚期糖基化终末产物对血神经屏障的影响

• 批准号: 22790821
• 负责人: SHIMIZU Fumitaka
• 金额: $ 1.5万
• 依托单位: Yamaguchi University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 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/grant/KAKENHI-PROJECT-22790821/
• 关键词: 血液神経関門; 後期糖化反応生成物; 糖尿病性末梢神経障害; 糖尿病性細小血管障害; ペリサイト; 末梢神経神経内膜内血管内皮細胞

The breakdown of the blood. nerve barrier(BNB) is considered to be a key step in diabetic neuropathy. Although basement membrane hypertrophy and breakdown of the BNB are characteristic features of diabetic neuropathy, the underlying pathogenesis remains unclear. The purpose of the present study was to identify the possible mechanisms responsible for inducing the hypertrophy of basement membrane and the disruption of the BNB after exposure to AGEs using our newly established human peripheral nerve microvascular endothelial cell(PnMEC) and pericyte cell lines. AGEs reduced the production of claudin-5 in PnMECs by increasing autocrine signalling through vascular endothelial growth factor(VEGF) secreted by the PnMECs themselves. Furthermore, AGEs increased the amount of fibronectin, collagen type IV and TIMP-1 in pericytes through a similar upregulation of autocrine VEGF and transforming growth factor(TGF)-released by pericytes. These results indicate that pericytes may be the main regulators of the basement membrane at the BNB. AGEs induce basement membrane hypertrophy and disrupt the BNB by increasing autocrine VEGF and TGF-signalling by pericytes under diabetic conditions.

血液的崩溃。神经屏障（BNB）被认为是糖尿病神经病的关键步骤。尽管基底膜肥大和BNB的分解是糖尿病神经病的特征，但潜在的发病机理仍不清楚。本研究的目的是确定使用我们新建立的人类周围神经微血管内皮细胞（PNMEC）和周细胞细胞系和周围的细胞系和周期细胞系，导致基底膜肥大的可能机制以及BNB的破坏。年龄通过PNMEC本身分泌的血管内皮生长因子（VEGF）来增加自分泌信号传导，从而降低了PNMEC中Claudin-5的产生。此外，年龄增加了周细胞中纤连蛋白，IV型和TIMP-1的量，通过类似的自分泌VEGF和转化生长因子（TGF）的类似上调（被周围的生长因子）。这些结果表明，周细胞可能是BNB基底膜的主要调节剂。年龄通过在糖尿病条件下通过周细胞增强自分泌VEGF和TGF-SIGNALLES来诱导基底膜肥大并破坏BNB。

项目成果

多巣性運動ニューロパチー血清が血液神経関門に及ぼす影響の解析

多灶性运动神经病血清对血神经屏障的影响分析

• 发表时间: 2011
• 作者: Hirotaka Matsuo;Tappei Takad;Kimiyoshi Ichida;et al.;清水文崇
• 通讯作者: 清水文崇

血管内皮異常

血管内皮异常

• 发表时间: 2011
• 作者: 清水文崇;神田隆
• 通讯作者: 神田隆

The effect of advanced glycation end-products on blood-nerve barrier.

晚期糖基化终产物对血神经屏障的影响。

• 发表时间: 2010
• 作者: 清水文崇;佐野泰照;斎藤和幸;春木明代;前田敏彦;安部真彰;神田隆;Fumitaka Shimizu
• 通讯作者: Fumitaka Shimizu

AGEによる血液神経関門破綻メカニズムの解析

AGEs引起血神经屏障破坏的机制分析

• 发表时间: 2010
• 作者: 清水文崇;神田隆
• 通讯作者: 神田隆

Advanced glycation end-products induce basement membrane hypertrophy in endoneurial microvessels and disrupt the blood-nerve barrier by stimulating the release of TGF-and vascular endothelial growth factor(VEGF) by pericytes

晚期糖基化终产物诱导神经内膜微血管基底膜肥大，并通过刺激周细胞释放 TGF 和血管内皮生长因子 (VEGF) 破坏血神经屏障

• 发表时间: 2011
• 期刊: Diabetologia
• 影响因子: 8.2
• 作者: Shimizu F;Sano Y;Haruki H;Kanda T
• 通讯作者: Kanda T