Acid-sensitive K+ channels as threrapeutic targets for immune diseases and cancers

2015 Fiscal Year Final Research Report

• 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
• 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

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.

Free Research Field

薬理系薬学