Inhibition of lung microbiota-derived proapoptotic peptides ameliorates acute exacerbation of pulmonary fibrosis

Corina N. D’Alessandro-Gabazza, Taro Yasuma, Tetsu Kobayashi, Masaaki Toda, Ahmed M. Abdel-Hamid, Hajime Fujimoto, Osamu Hataji, Hiroki Nakahara, Atsuro Takeshita, Kota Nishihama, Tomohito Okano, Haruko Saiki, Yuko Okano, Atsushi Tomaru, Valeria Fridman D’Alessandro, Miyako Shiraishi, Akira Mizoguchi, Ryoichi Ono, Junpei Ohtsuka, Masayuki FukumuraTetsuya Nosaka, Xuenan Mi, Diwakar Shukla, Kensuke Kataoka, Yasuhiro Kondoh, Masaki Hirose, Toru Arai, Yoshikazu Inoue, Yutaka Yano, Roderick I. Mackie, Isaac Cann, Esteban C. Gabazza

Research output: Contribution to journalArticlepeer-review

Abstract

Idiopathic pulmonary fibrosis is an incurable disease of unknown etiology. Acute exacerbation of idiopathic pulmonary fibrosis is associated with high mortality. Excessive apoptosis of lung epithelial cells occurs in pulmonary fibrosis acute exacerbation. We recently identified corisin, a proapoptotic peptide that triggers acute exacerbation of pulmonary fibrosis. Here, we provide insights into the mechanism underlying the processing and release of corisin. Furthermore, we demonstrate that an anticorisin monoclonal antibody ameliorates lung fibrosis by significantly inhibiting acute exacerbation in the human transforming growth factorβ1 model and acute lung injury in the bleomycin model. By investigating the impact of the anticorisin monoclonal antibody in a general model of acute lung injury, we further unravel the potential of corisin to impact such diseases. These results underscore the role of corisin in the pathogenesis of acute exacerbation of pulmonary fibrosis and acute lung injury and provide a novel approach to treating this incurable disease.

Original languageEnglish (US)
Article number1558
JournalNature communications
Volume13
Issue number1
DOIs
StatePublished - Dec 2022

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy

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