An attempt to elucidate the pathophysiology of idiopathic pulmonary fibrosis using type I alveolar epithelium-derived substance RAGE

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09655
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Hiroshima University
• Principal Investigator: Iwamoto Hiroshi 広島大学, 医系科学研究科(医), 講師 (60457398)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 特発性肺線維症 / 間質性肺炎 / 急性増悪 / バイオマーカー / 治療薬

Outline of Final Research Achievements

HMGB1 (high mobility group box-1 protein), which is secreted extracellularly when cells are damaged, is elevated in the blood of patients with intractable disease called idiopathic pulmonary fibrosis (IPF). Moreover, IPF patients with higher HMGB1 had higher risk of acute exacerbation. esRAGE (endogenous secretory receptor for advanced glycation end product), which binds to HMGB1 and suppress its effect, is decreased in patients with IPF. Moreover, IPF patients with lower esRAGE levels had poorer survival. In mouse pneumonitis model experiment, it was found that RAGE inhibitor can be applied to the treatment of pneumonitis.

Free Research Field

呼吸器内科

Academic Significance and Societal Importance of the Research Achievements

今回の研究結果から、難病である特発性肺線維症患者の血中HMGB1、esRAGEを測定することにより、患者の予後や急性増悪の予測、急性増悪を起こした際の予後予測など、治療の適応を判断する上で重要な疾患進行の予測出来たことから、新規の血液検査としての可能性が示された。また動物実験の結果からはこのHMGB1、RAGEが関わる分子機構が特発性肺線維症の治療にも応用できる可能性が示され、新規治療薬の開発の一歩を示した。