Acid-sensitive K+ channels as threrapeutic targets for immune diseases and cancers
Project/Area Number |
25460111
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Pharmacology in pharmacy
|
Research Institution | Kyoto Pharmaceutical University |
Principal Investigator |
Ohya Susumu 京都薬科大学, 薬学部, 教授 (70275147)
|
Co-Investigator(Kenkyū-buntansha) |
FUJII Masanori 京都薬科大学, 薬学部, 准教授 (40434667)
|
Project Period (FY) |
2013-04-01 – 2016-03-31
|
Project Status |
Completed (Fiscal Year 2015)
|
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)
|
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 |
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.
|
Report
(4 results)
Research Products
(60 results)
-
-
-
-
-
[Journal Article] Pathophysiological significance of the two-pore domain K(+) channel K2P5.1 in splenic CD4(+)CD25(-) T cell subset from a chemically-induced murine inflammatory bowel disease model.2015
Author(s)
Nakakura S, Matsui M, Sato A, Ishii M, Endo K, Muragishi S, Murase M, Kito H, Niguma H, Kurokawa N, Fujii M, Araki M, Araki K, Ohya S.
-
Journal Title
Frontiers in Physiology
Volume: 6
Pages: 299-299
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
[Journal Article] Up-regulation of KCa3.1 K^+ channel in mesenteric lymph node CD4^+ T-lymphocytes from a mouse model of dextran sodium sulfate-induced inflammatory bowel disease2014
Author(s)
Ohya S, Fukuyo Y, Kito H, Shibaoka R, Matsui M, Niguma H, Maeda Y, Yamamura H, Fujii M, Kimura K, Imaizumi Y
-
Journal Title
Am J Physiol Gastrointest Liver Physiol
Volume: in press
Issue: 10
Pages: G873-G885
DOI
Related Report
Peer Reviewed
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-