2011 Fiscal Year Final Research Report
Roles of fibroblast Na^+/Ca^<2+> exchangers in fibrosis
| Project/Area Number |
21590288
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | Fukushima Medical University |
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Principal Investigator |
KIMURA Junko 福島県立医科大学, 医学部, 教授 (10186322)
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| Project Period (FY) |
2009 – 2011
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| Keywords | 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 |
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| Research Abstract |
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.
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