Aggresome-selective autophagy (aggrephagy) by TOLLIP in IPF.

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08666
• 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: Kaneko Yumi 東京慈恵会医科大学, 医学部, 講師 (50646669)
• Co-Investigator(Kenkyū-buntansha): 荒屋 潤 東京慈恵会医科大学, 医学部, 教授 (90468679)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: TOLLIP / 特発性肺線維症（IPF） / 遺伝子多型 / 環境因子 / アグリゾーム / アグリファジー

Outline of Final Research Achievements

TOLLIP plays important roles in not only TLR signaling pathway, but also aggresome-selective autophagy (aggrephagy). Insufficient autophagy is involved in the pathogenesis of IPF, hence, we hypothesized that decreased TOLLIP expression might contribute to IPF pathogenesis by determinating cell fate through stress-induced aggresome accumulation. TOLLIP expression in bronchial epithelia was decreased in IPF by immunohistochemistry. Kockdown of TOLLIP in isolated epithelial cells promoted cigarette smoke-induced cell death and aggresome accumulation. Decreased TOLLIP expression and subsequent aggresome accumulation and accelerated cell death might be associated with IPF pathogenesis.

Free Research Field

間質性性肺疾患

Academic Significance and Societal Importance of the Research Achievements

TOLLIPの役割を、自然免疫応答や蛋白凝集体制御による細胞運命の規定の点から明らかにすることで、IPF病態の理解と解明が進み、治療法開発はのみならず、予防についての新たな観点の発見につなげられる事も期待される。