Microbiota-derived corisin accelerates kidney fibrosis by promoting cellular aging

Taro Yasuma, Hajime Fujimoto, Corina N. D’Alessandro-Gabazza, Masaaki Toda, Mei Uemura, Kota Nishihama, Atsuro Takeshita, Valeria Fridman D’Alessandro, Tomohito Okano, Yuko Okano, Atsushi Tomaru, Tomoko Anoh, Chisa Inoue, Manal A. B. Alhawsawi, Ahmed M. Abdel-Hamid, Kyle Leistikow, Michael R. King, Ryoichi Ono, Tetsuya Nosaka, Hidetoshi Yamazaki, Christopher J. Fields, Roderick I. Mackie, Xuenan Mi, Diwakar Shukla, Justine Arrington, Yutaka Yano, Osamu Hataji, Tetsu Kobayashi (), Isaac Cann () and Esteban C. Gabazza ()
Additional contact information
Taro Yasuma: Edobashi 2-174
Hajime Fujimoto: Edobashi 2-174
Corina N. D’Alessandro-Gabazza: Edobashi 2-174
Masaaki Toda: Edobashi 2-174
Mei Uemura: Edobashi 2-174
Kota Nishihama: Edobashi 2-174
Atsuro Takeshita: Edobashi 2-174
Valeria Fridman D’Alessandro: Edobashi 2-174
Tomohito Okano: Edobashi 2-174
Yuko Okano: Edobashi 2-174
Atsushi Tomaru: Edobashi 2-174
Tomoko Anoh: Edobashi 2-174
Chisa Inoue: Edobashi 2-174
Manal A. B. Alhawsawi: University of Illinois Urbana-Champaign
Ahmed M. Abdel-Hamid: University of Illinois Urbana-Champaign
Kyle Leistikow: 7420 S Howell Ave
Michael R. King: 7420 S Howell Ave
Ryoichi Ono: Edobashi 2-174
Tetsuya Nosaka: Edobashi 2-174
Hidetoshi Yamazaki: Edobashi 2-174
Christopher J. Fields: University of Illinois Urbana-Champaign
Roderick I. Mackie: University of Illinois Urbana-Champaign
Xuenan Mi: University of Illinois Urbana-Champaign
Diwakar Shukla: University of Illinois Urbana-Champaign
Justine Arrington: University of Illinois Urbana-Champaign
Yutaka Yano: Edobashi 2-174
Osamu Hataji: Tonomachi 1550
Tetsu Kobayashi: Edobashi 2-174
Isaac Cann: University of Illinois Urbana-Champaign
Esteban C. Gabazza: Edobashi 2-174

Nature Communications, 2025, vol. 16, issue 1, 1-29

Abstract: Abstract The increasing global prevalence of diabetic nephropathy poses substantial health and economic burdens. Currently, effective anti-fibrotic therapies for managing kidney fibrosis associated with chronic kidney disease are lacking. This study reveals corisin, a microbiota-derived peptide, as a central driver in the progression of diabetic kidney fibrosis. Corisin levels were found to be markedly elevated in the serum of diabetic chronic kidney disease patients relative to healthy controls, with strong correlations to advanced disease stages and declining renal function. In a murine model of kidney fibrosis, corisin levels were similarly heightened, directly contributing to increased inflammation and worsening fibrosis and renal impairment. Notably, the use of a monoclonal anti-corisin antibody significantly reduced nephropathy severity in diabetic mice. Through molecular dynamics simulations and experimental validation, we demonstrated that corisin interacts with human serum albumin, potentially enhancing its renal accumulation and pathological impact. The pathogenic mechanism of corisin involves the acceleration of cellular senescence and the induction of epithelial-mesenchymal transition and apoptosis in kidney cells. These findings underscore the critical role of corisin in progressive diabetic nephropathy and suggest a promising new target for therapeutic intervention.

Date: 2025
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DOI: 10.1038/s41467-025-61847-2

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