| Project/Area Number |
25460111
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pharmacology in pharmacy
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| Research Institution | Kyoto Pharmaceutical University |
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Principal Investigator |
Ohya Susumu 京都薬科大学, 薬学部, 教授 (70275147)
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| Co-Investigator(Kenkyū-buntansha) |
FUJII Masanori 京都薬科大学, 薬学部, 准教授 (40434667)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | イオンチャネル / カリウムチャネル / 炎症性腸疾患 / Tリンパ球 / スプライシング阻害 / 癌細胞増殖 / 炎症腸疾患 / pH感受性カリウムチャネル / K2P5.1 / 選択的スプライシング / スプライシング阻害剤 / 機能制御分子 / リンパ球 / Ｋ２Ｐ５．１ |
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| Outline of Final Research Achievements |
The two-pore domain K+ (K2P) channels are possible therapeutic targets for autoimmune diseases and several cancers. We elucidate the pathological significance of the K2P5.1 K+ channel in inflammatory bowel disease (IBD). Significant upregulation of K2P5.1 K+ channel were observed in the CD4+ T cells of the IBD model. The knockout of K2P5.1 in mice significantly suppressed the disease severity in the IBD model. Additionally, we identified an N-terminus-lacking, novel splicing isoform of K2P5.1 K+ channel, K2P5.1B from the human lymphoid tissues. In a heterologous expression system, K2P5.1B inhibited the plasma membrane trafficking of K2P5.1A. The pre-mRNA splicing inhibitor significantly enhanced the expression levels of K2P5.1B in human leukemic K562 cells, resulting in decrease in the K2P5.1 activity. The pre-mRNA splicing mechanism underlying the posttranscriptional regulation of K2P5.1 K+ channel may be a new therapeutic strategy for autoimmune diseases and cancers.
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