Usefulness of lymphocyte Kv1.3 channels in chronic inflammatory disease

2020 Fiscal Year Final Research Report

• Project/Area Number: 16K08484
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General physiology
• Research Institution: Miyagi University (2019-2020); Tohoku University (2016-2018)
• Principal Investigator: KAZAMA ITSURO 宮城大学, 看護学群, 教授 (60593978)
• Project Period (FY): 2016-04-01 – 2021-03-31
• Keywords: 慢性炎症性疾患 / リンパ球Kv1.3 / 慢性腎臓病 / 線維化

Outline of Final Research Achievements

The overexpression of lymphocyte Kv1.3-channels contributes to the progression of chronic kidney disease (CKD) by promoting cellular proliferation and interstitial fibrosis. In our patch-clamp studies, since benidipine and simvastatin were highly potent as Kv1.3-channel inhibitors, they could exert therapeutic efficacy in the progression of CKD. Therefore, using a rat model with advanced stage chronic renal failure (advanced CRF), we examined the effects of these drugs on the histopathological features of the kidneys and the cortical expression of pro-inflammatory cytokines. In the cortical interstitium of advanced CRF rat kidneys, these drugs significantly ameliorated the progression of renal fibrosis. Both drugs reduced the number of proliferating leukocytes with a significant decrease in the pro-inflammatory cytokine expression. The studies indicated the therapeutic potency of Kv1.3-channel inhibitors in the treatment or the prevention of chronic inflammatory disease.

Free Research Field

生理学一般、病態生理学

Academic Significance and Societal Importance of the Research Achievements

本研究により、慢性閉塞性肺疾患や炎症性腸疾患、外傷・手術後の瘢痕、全身性炎症反応症候群・敗血症などの疾患動物モデルに対するKv1.3阻害薬の効果が明らかになれば、ヒトに対する臨床試験など、治療の実用化に向けた共同研究へと駒を進めていくことが可能になる。