Roles of fibroblast Na^+/Ca^<2+> exchangers in fibrosis

成纤维细胞Na^/Ca^2交换器在纤维化中的作用

• 批准号: 21590288
• 负责人: KIMURA Junko
• 金额: $ 2.83万
• 依托单位: Fukushima Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21590288/
• 关键词: 心臓; 線維芽細胞; 低酸素; TRPM2; N^a+/Ca^<2+>交換輸送体; 過酸化水素; 細胞内Ca^<2+>; ラット; ADPリボース; Na^+/Ca^<2+>交換輸送体; クロトリマゾール; siRNA; H_2O_2; Na^+; Ca^<2+>交換輸送体; 骨格筋; KB-R7943; SEA0400; Ca^<2+>交換輸送体阻害薬; 遊走; 創傷治癒

We studies the effect of hypoxia on the expression levels of Na^+/Ca^<2+> exchangers and transient receptor potential melastatin(TRPM2) channels in cardiac fibroblasts obtained primarily from rat hearts. Cardiac fibroblasts were cultured under hypoxic condition for 24 hours using Aneropac. When the hypoxia-exposed cells were whole-cell clamped, significant increase in membrane current was observed. The current was a non-selective cation current and was inhibited by clotrimazole, indicating that curren is likely TRPM2 current. mRNA analysis indicated increase in TRPM2 expression in hypoxia exposed fibroblasts. When siRNA was introduced in the cells, hypoxia did not increase the nonselective cation current nor TRPM2 mRNA. H_2O_2 is an activator of TRPM2. When hypoxia-exposed cells were fura-2 loaded, H_2O_2(300μM) increased intracellular Ca^<2+> concentration significantly in hypoxia-exposed fibroblasts but not in normoxia-exposed control cells. Na^+/Ca^<2+> exchanger expression was decreased by hypoxia exposure. We concluded that hypoxia increase TRPM2 expression but decrease Na^+/Ca^<2+> exchanger expression in cardiac fibroblasts. These phenomena may contribute to activation of fibroblasts and acceleration of fibrosis after hypoxia in the heart.

我们研究了缺氧对主要从大鼠心脏获得的心脏成纤维细胞中Na^+/Ca^<2+>交换器和瞬态接收器电位曲霉（TRPM2）通道的影响。使用Aneropac在低氧条件下在低氧条件下培养心脏成纤维细胞。当将低氧细胞全细胞夹紧时，观察到膜电流的显着增加。电流是非选择性阳离子电流，被克洛咪唑抑制，表明咖喱可能是TRPM2电流。 mRNA分析表明，缺氧暴露的成纤维细胞中TRPM2表达增加。当在细胞中引入siRNA时，缺氧并没有增加非选择性阳离子电流和TRPM2 mRNA。 H_2O_2是TRPM2的激活剂。当暴露于低氧细胞Fura-2加载时，H_2O_2（300μM）在缺氧暴露的成纤维细胞中显着增加了细胞内Ca^<2+>浓度，而在暴露于常氧的对照细胞中则增加了。 Na^+/Ca^<2+>通过缺氧暴露降低交换器的表达。我们得出的结论是，缺氧会增加TRPM2的表达，但降低了心脏成纤维细胞中的Na^+/Ca^<2+>交换器的表达。这些现象可能导致心脏缺氧后成纤维细胞的激活和纤维化的加速。

项目成果

長期ニコチン受容体刺激により誘発される生体機能変化:Na^+/Ca^<2+>交換輸送体の発現量の変化

长期烟碱受体刺激引起的生物功能变化：Na^+/Ca^2+交换转运蛋白表达水平的变化

• 发表时间: 2011
• 期刊: 医学のあゆみ
• 作者: 池上瑶子;他;木村純子
• 通讯作者: 木村純子

Na/Ca exchanger is involved in migration and contraction of rat rat tenocytes

Na/Ca交换器参与大鼠肌腱细胞的迁移和收缩

• 发表时间: 2009
• 作者: Sakamoto K;Owada Y;Shikama Y;Wada I;Waguri S;Kimura J
• 通讯作者: Kimura J

スタチン誘発性骨格筋毒性へのトランスポーターの関与

转运蛋白参与他汀类药物诱导的骨骼肌毒性

• 发表时间: 2009
• 作者: 坂本多穂;木村純子
• 通讯作者: 木村純子

Hypoxic stress induces TRPM2 channel expression in adult rat cardiac fibroblasts

缺氧应激诱导成年大鼠心脏成纤维细胞TRPM2通道表达

• 发表时间: 2011
• 作者: Kenji TAKAHASHIi;Kazuho SAKAMOTO and Junko KIMURA
• 通讯作者: Kazuho SAKAMOTO and Junko KIMURA

Effects of intrarenal administration on Na^+/Ca^<2+> exchanger 1 inhibitor SEA0400 in rats

肾内给药对大鼠Na^/Ca^2交换器1抑制剂SEA0400的影响

• 发表时间: 2011
• 作者: YATABE Midori;YATABE Junichi;WATANABE Tsuyoshi and KIMURA Junko
• 通讯作者: WATANABE Tsuyoshi and KIMURA Junko