the role of endoplasmic reticulum selective autophagy in the pathogenesis of idiopathic pulmonary fibrosis

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08528
• 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: Jikei University School of Medicine
• Principal Investigator: NUMATA Takanori 東京慈恵会医科大学, 医学部, 准教授 (30366257)
• Co-Investigator(Kenkyū-buntansha): 原 弘道 東京慈恵会医科大学, 医学部, 教授 (70398791)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: オートファジー / 特発性肺線維症 / 小胞体

Outline of Final Research Achievements

Endoplasmic reticulum (ER) stress induced by accumulation of intracellular damaged protein is increased in lung epithelial cell in IPF (Idiopathic pulmonary fibrosis). Excessive ER stress promotes lung fibrosis by inducing epithelial cell death and cell senescence. It is likely that ERphagy (ER-selective autophagy) alleviates ER stress response and inhibits lung fibrosis. In this study, we demonstrated that expression of TEX264 (an adaptor protein that Connects ER with LC3) was decreased in IPF lung. Suppression of ERphagy by knockdown of TEX264 promoted ER stress-induced epithelial cell death and TGF-beta induced myofibroblast differentiation. Decreased ERphagy in IPF may play important roles in IPF pathogenesis.

Free Research Field

呼吸器

Academic Significance and Societal Importance of the Research Achievements

特発性肺線維症（idiopathic interstitial pneumonia:IPF）では過剰なERストレスが病態に重要であることがこれまでの報告で明らかとなっていたが、治療的介入は困難であった。本検討にてERファジーの低下が病態に関連することが明らかとなり、ERファジーの促進がIPFの治療の新たな選択肢となる可能性が示唆された。