Development of treatment for idiopathic pulmonary fibrosis targeting bacterial-derived apoptosis-promoting peptides

• Project/Area Number: 21K16116
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Mie University
• Principal Investigator: Yasuma Taro 三重大学, 医学部附属病院, 助教 (80773887)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2022: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2021: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 特発性肺線維症 / 細菌叢 / アポトーシス / 肺線維症 / 急性肺障害

Outline of Research at the Start

特発性肺線維症（IPF）は慢性進行性に肺線維化をきたす致死的な肺疾患である。IPFにおいて、肺上皮細胞のアポトーシスが疾患の進行に重要な役割を果たす。我々は細菌由来アポトーシス促進ペプチドがIPFの病態に関与することを発見した。本研究は肺線維症マウスに本ペプチドに対するモノクローナル抗体を投与して病態を抑制しうるかを検討し、新しいIPF治療薬としての可能性を見出すことを目的とする。

Outline of Final Research Achievements

Idiopathic pulmonary fibrosis is an incurable disease of unknown etiology. We recently identified corisin, a proapoptotic peptide that triggers acute exacerbation of pulmonary fibrosis. In this study, we prepared a monoclonal antibody that suppresses the activity of corisin and verified its effect on a pulmonary fibrosis mouse model. We have shown that an anticorisin monoclonal antibody ameliorates inflammation, fibrosis and apoptosis of alveolar epithelial cells in the human transforming growth factorβ1 model and the bleomycin model. These results underscore the role of corisin in the pathogenesis of acute exacerbation of pulmonary fibrosis and provide a novel approach to treating this incurable disease.

Academic Significance and Societal Importance of the Research Achievements

IPFの病態に細菌叢が関与することが報告されてきたが、詳細な分子機構は不明であった。我々は、細菌叢由来のペプチドであるcorisinが肺線維症の病態進行や急性増悪に関与することを初めて明らかにした。これは細菌がペプチドの放出を介して病態に直接的に関与することを示している。本研究成果は、難治性疾患であるIPFの新規治療や新規バイオマーカーの開発につながりうる、大変有意義な研究成果であると考える。

Research Products

• [Int'l Joint Research] イリノイ大学アーバナシャンペーン校(米国)
• [Journal Article] Inhibition of a Microbiota-Derived Peptide Ameliorates Established Acute Lung Injury (2023)
  • Author(s): D'Alessandro Fridman V, D'Alessandro-Gabazza CN, Yasuma T, Toda M, Takeshita A, Tomaru A, Tharavecharak S, Lasisi IO, Hess RY, Nishihama K, Fujimoto H, Kobayashi T, Cann I, Gabazza EC.
  • Journal Title: American Journal of Pathology Volume: 23 Issue: 6 Pages: 740-754
  • DOI: 10.1016/j.ajpath.2023.03.003
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Inhibition of lung microbiota-derived proapoptotic peptides ameliorates acute exacerbation of pulmonary fibrosis. (2022)
  • Author(s): D'Alessandro-Gabazza CN, Yasuma T, Kobayashi T, Toda M, Abdel-Hamid AM, Fujimoto H, Hataji O, Nakahara H, Takeshita A, Nishihama K, Okano T, Saiki H, Okano Y, Tomaru A, D'Alessandro VF, Shiraishi M, Mizoguchi A, Ono R, Ohtsuka J, Fukumura M, Nosaka T, et al. & Gabazza EC
  • Journal Title: Nat Commun Volume: 13 Issue: 1 Pages: 1558-1558
  • DOI: 10.1038/s41467-022-29064-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Complete Genome Sequences of Three Staphylococcus haemolyticus Strains Isolated from the Lung of a TGFβ1 Transgenic Mouse with Lung Fibrosis (2022)
  • Author(s): Abdel-Hamid AM, D'Alessandro-Gabazza CN, Yasuma T, Walden KKO, Fields CJ, Gabazza EC, Cann I.
  • Journal Title: Microbiology Resource Announcements Volume: 11 Issue: 4
  • DOI: 10.1128/mra.01176-21
  • Peer Reviewed / Open Access / Int'l Joint Research