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+ 交换剂和瞬时受体电位褪黑素(TRPM2)通道表达水平的影响。使用 Aneropac 在缺氧条件下培养心脏成纤维细胞 24 小时。当将缺氧暴露的细胞进行全细胞钳夹时，观察到膜电流显着增加。该电流为非选择性阳离子电流，并被克霉唑抑制，表明该电流很可能是TRPM2电流。 mRNA 分析表明缺氧暴露的成纤维细胞中 TRPM2 表达增加。当将 siRNA 引入细胞时，缺氧不会增加非选择性阳离子电流，也不会增加 TRPM2 mRNA。 H_2O_2 是 TRPM2 的激活剂。当缺氧暴露的细胞负载fura-2时，H_2O_2(300μM)显着增加缺氧暴露的成纤维细胞中的细胞内Ca^2+浓度，但在常氧暴露的对照细胞中没有显着增加。 Na ^+ /Ca ^ 2+ 交换体表达因缺氧暴露而降低。我们得出结论，缺氧会增加心肌成纤维细胞中TRPM2的表达，但会降低Na^+/Ca^2+交换器的表达。这些现象可能有助于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

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

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