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Decreased expression of OATP2a1 in porcine pancreas elastase-induced COPD mouse model.

Research Project

Project/Area Number 19K16433
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 47060:Clinical pharmacy-related
Research InstitutionFukuoka University

Principal Investigator

Matsumoto Junichi  福岡大学, 薬学部, 助教 (10550064)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords血液脳関門 / COPD / 慢性閉塞性肺疾患 / BBB / extracellular vesicle / エクソソーム / 細胞外小胞
Outline of Research at the Start

慢性閉塞性肺疾患(COPD)患者は、情動障害・認知機能障害などの中枢性合併症を併発する。この中枢性合併症は、COPD患者の予後不良とQOL低下の重大な危険因子となるが、その対策は不十分である。申請者は、COPDモデルマウスで血液脳関門(BBB)が障害されることや認知機能障害を誘発する抗コリン薬の脳内移行が増加することを突き止めた。そこで、『COPD病態下ではBBB機能障害を契機にして、脳の脆弱化と治療薬剤の中枢性副作用の2要素が複合化し、脳機能障害を顕在化あるいは増悪化させる』との仮説を立証する。

Outline of Final Research Achievements

Chronic obstructive pulmonary disease (COPD) frequently coexists with comorbidities such as cardiovascular disease, anxiety and depression, and cognitive dysfunction. The Blood-brain barrier (BBB) is a highly selective semipermeable barrier structure that maintains the homeostasis in the central nervous system. BBB impairments are related to various dysfunction including anxiety, depression and cognitive dysfunction in the brain disorders. In this study, we quantified the mRNA expression of SLC transporters, ABC transporters and tight junction-related proteins in porcine pancreas elastase (PPE)-inhaled COPD model mouse. The mRNA expression of OATPs in PPE-inhaled mice is significantly decreased compared with PBS-inhaled mice. Although we directly indicated the decrease of OATPS in the brain contributes to brain dysfunctions in our model mouse, the alteration of transporters affects molecular trafficking across the BBB, leading to brain dysfunction in COPD pathogenesis.

Academic Significance and Societal Importance of the Research Achievements

COPD患者では、不安・抑うつなど情動障害や認知機能低下が併発する。血液脳関門は循環血液と脳実質を隔てる「障壁」として機能するだけでなく、正常な脳機能維持に必要な物質輸送も担っている。本研究では、COPDモデルの脳トランスポーター発現量においてOATP2a1が減少していた。OATP2a1はプロスタグランジン(PG)の取込み輸送体であるため、COPD病態下において、脳内PGクリアランスが異常化する可能性がある。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (2 results)

All 2021

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (1 results)

  • [Journal Article] Testosterone deficiency promotes the development of pulmonary emphysema in orchiectomized mice exposed to elastase2021

    • Author(s)
      Aono K, Matsumoto J, Nakagawa S, Matsumoto T, Koga M, Migita K, Tominaga K, Sakai Y, Yamauchi A.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 558 Pages: 94-101

    • DOI

      10.1016/j.bbrc.2021.04.051

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed
  • [Presentation] 精巣摘出マウスにおけるテストステロン欠乏に伴う胸腺の変化と肺気腫形成の関連性2021

    • Author(s)
      青野健太郎、松本純一、河村莉奈、松本太一、右田啓介、道具伸也、山内淳史
    • Organizer
      次世代を担う若手のための創薬・医療薬理シンポジウム2021
    • Related Report
      2021 Annual Research Report

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Published: 2019-04-18   Modified: 2023-01-30  

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