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

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16433
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Fukuoka University
• Principal Investigator: Matsumoto Junichi 福岡大学, 薬学部, 助教 (10550064)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 血液脳関門 / COPD

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.

Free Research Field

薬理学

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。