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 Fukumura, Tetsuya Nosaka, Xuenan Mi, Diwakar Shukla, Kensuke Kataoka, Yasuhiro Kondoh, Masaki Hirose, Toru Arai, Yoshikazu Inoue, Yutaka Yano, Roderick I. Mackie, Isaac Cann () and Esteban C. Gabazza ()
Additional contact information
Corina N. D’Alessandro-Gabazza: Mie University Faculty and Graduate School of Medicine
Taro Yasuma: Mie University Faculty and Graduate School of Medicine
Tetsu Kobayashi: Mie University Faculty and Graduate School of Medicine
Masaaki Toda: Mie University Faculty and Graduate School of Medicine
Ahmed M. Abdel-Hamid: University of Illinois at Urbana–Champaign
Hajime Fujimoto: Mie University Faculty and Graduate School of Medicine
Osamu Hataji: Matsusaka Municipal Hospital
Hiroki Nakahara: Mie University Faculty and Graduate School of Medicine
Atsuro Takeshita: Mie University Faculty and Graduate School of Medicine
Kota Nishihama: Mie University Faculty and Graduate School of Medicine
Tomohito Okano: Mie University Faculty and Graduate School of Medicine
Haruko Saiki: Mie University Faculty and Graduate School of Medicine
Yuko Okano: Mie University Faculty and Graduate School of Medicine
Atsushi Tomaru: Mie University Faculty and Graduate School of Medicine
Valeria Fridman D’Alessandro: Mie University Faculty and Graduate School of Medicine
Miyako Shiraishi: University of Illinois at Urbana–Champaign
Akira Mizoguchi: Mie University Graduate School of Medicine
Ryoichi Ono: Mie University Graduate School of Medicine
Junpei Ohtsuka: Mie University Graduate School of Medicine
Masayuki Fukumura: Mie University Graduate School of Medicine
Tetsuya Nosaka: Mie University Graduate School of Medicine
Xuenan Mi: University of Illinois at Urbana-Champaign
Diwakar Shukla: University of Illinois at Urbana-Champaign
Kensuke Kataoka: Tosei General Hospital
Yasuhiro Kondoh: Tosei General Hospital
Masaki Hirose: National Hospital Organization Kinki-Chuo Chest Medical Center
Toru Arai: National Hospital Organization Kinki-Chuo Chest Medical Center
Yoshikazu Inoue: National Hospital Organization Kinki-Chuo Chest Medical Center
Yutaka Yano: Mie University Faculty and Graduate School of Medicine
Roderick I. Mackie: University of Illinois at Urbana–Champaign
Isaac Cann: University of Illinois at Urbana–Champaign
Esteban C. Gabazza: Mie University Faculty and Graduate School of Medicine

Nature Communications, 2022, vol. 13, issue 1, 1-23

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-29064-3

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