Pathological study of IPF acute exacerbation for drug discovery: Focusing on steroid refractory signal transduction pathway

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08156
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Tokai University
• Principal Investigator: ITO YOKO 東海大学, 医学部, 准教授 (90286451)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 肺胞上皮細胞 / 急性肺障害 / ステロイド

Outline of Final Research Achievements

Acute exacerbation (AE) is the worst prognostic factor in patients with idiopathic pulmonary fibrosis (IPF), which is empirically treated by glucocorticosteroid. However, the effect of glucocorticosteroid is not enough for the patients to recover completely. In this study, 1) we could establish the isolation and culture systems of rat alveolar epithelial cells in my new research laboratory. We have found 2)dysfunction of alveolar epithelial cells induced by endoplasmic reticulum stress was not restored by glucocorticosteroid, 3) irradiation, which causes AE, to alveolar epithelial cells led to epithelial barrier dysfunction, and 4) LPS, which also leads to AE, changed many gene expressions in alveolar epithelial cells, which were not abrogated by glucocorticosteroid.

Free Research Field

肺胞上皮細胞傷害と修復

Academic Significance and Societal Importance of the Research Achievements

本研究の成果から、特発性肺線維症の病態に関与する小胞体という細胞内小器官のストレスや急性増悪を引き起こす因子（放射線、LPS:細菌の構造の一部で炎症を惹起）が肺胞上皮細胞傷害を引き起こすが、ステロイドではその肺胞上皮細胞傷害の予防・修復が完全にはできないことが判ってきた。今後、本研究の成果をさらに発展させることで、本研究開始当初の目的であった、特発性肺線維症の急性増悪に対してステロイドにプラスした新たな治療法を発見することができる可能性がある。