2. Academic Validation
  3. Microbiota-derived corisin accelerates kidney fibrosis by promoting cellular aging

Microbiota-derived corisin accelerates kidney fibrosis by promoting cellular aging

  • Nat Commun. 2025 Aug 25;16(1):7591. doi: 10.1038/s41467-025-61847-2.
Taro Yasuma # 1 2 3,  Hajime Fujimoto # 4,  Corina N D'Alessandro-Gabazza # 1 2 5,  Masaaki Toda # 1,  Mei Uemura 3,  Kota Nishihama 1 3,  Atsuro Takeshita 1 3,  Valeria Fridman D'Alessandro 1 2,  Tomohito Okano 4,  Yuko Okano 3,  Atsushi Tomaru 4,  Tomoko Anoh 1 4,  Chisa Inoue 3,  Manal A B Alhawsawi 5 6,  Ahmed M Abdel-Hamid 5,  Kyle Leistikow 7,  Michael R King 7,  Ryoichi Ono 8,  Tetsuya Nosaka 8,  Hidetoshi Yamazaki 9,  Christopher J Fields 10,  Roderick I Mackie 5 6 11,  Xuenan Mi 12,  Diwakar Shukla 12,  Justine Arrington 13,  Yutaka Yano 3,  Osamu Hataji 14,  Tetsu Kobayashi 15 16,  Isaac Cann 17 18 19 20 21 22,  Esteban C Gabazza 23 24 25 26 27
Affiliations

Affiliations

  • 1 Department of Immunology, Mie University Faculty and Graduate School of Medicine, Edobashi 2-174, Tsu, Mie, Japan.
  • 2 Microbiome Research Center, Mie University, Edobashi 2-174, Tsu, Mie, Japan.
  • 3 Department of Diabetes, Metabolism and Endocrinology, Mie University Faculty and Graduate School of Medicine, Edobashi 2-174, Tsu, Mie, Japan.
  • 4 Department of Pulmonary and Critical Care Medicine, Mie University Faculty and Graduate School of Medicine, Edobashi 2-174, Tsu, Mie, Japan.
  • 5 Carl R. Woese Institute for Genomic Biology (Microbiome Metabolic Engineering), University of Illinois Urbana-Champaign, Urbana, IL, USA.
  • 6 Division of Nutritional Sciences, University of Illinois Urbana-Champaign, Urbana, IL, USA.
  • 7 Microbial Discovery Group, 7420 S Howell Ave, Oak Creek, WI, USA.
  • 8 Department of Microbiology and Molecular Genetics, Mie University Graduate School of Medicine, Edobashi 2-174, Tsu, Mie, Japan.
  • 9 Department of Stem Cell and Developmental Biology, Mie University Graduate School of Medicine, Edobashi 2-174, Tsu, Mie, Japan.
  • 10 W.M. Keck Center for Functional and Comparative Genomics, University of Illinois Urbana-Champaign, Urbana, IL, USA.
  • 11 Department of Animal Science, University of Illinois Urbana-Champaign, Urbana, IL, USA.
  • 12 Department of Chemical and Biomolecular Engineering, University of Illinois Urbana-Champaign, Urbana, IL, USA.
  • 13 Roy J. Carver Biotechnology Center, University of Illinois Urbana-Champaign, Urbana, IL, USA.
  • 14 Respiratory Center, Matsusaka Municipal Hospital, Tonomachi 1550, Matsusaka, Mie, Japan.
  • 15 Microbiome Research Center, Mie University, Edobashi 2-174, Tsu, Mie, Japan. [email protected].
  • 16 Department of Pulmonary and Critical Care Medicine, Mie University Faculty and Graduate School of Medicine, Edobashi 2-174, Tsu, Mie, Japan. [email protected].
  • 17 Carl R. Woese Institute for Genomic Biology (Microbiome Metabolic Engineering), University of Illinois Urbana-Champaign, Urbana, IL, USA. [email protected].
  • 18 Division of Nutritional Sciences, University of Illinois Urbana-Champaign, Urbana, IL, USA. [email protected].
  • 19 Department of Animal Science, University of Illinois Urbana-Champaign, Urbana, IL, USA. [email protected].
  • 20 The School of Molecular and Cellular Biology, University of Illinois Urbana-Champaign, Urbana, IL, USA. [email protected].
  • 21 Department of Microbiology, University of Illinois Urbana-Champaign, Urbana, IL, USA. [email protected].
  • 22 Center for East Asian & Pacific Studies, University of Illinois Urbana-Champaign, Urbana, IL, USA. [email protected].
  • 23 Department of Immunology, Mie University Faculty and Graduate School of Medicine, Edobashi 2-174, Tsu, Mie, Japan. [email protected].
  • 24 Microbiome Research Center, Mie University, Edobashi 2-174, Tsu, Mie, Japan. [email protected].
  • 25 Department of Pulmonary and Critical Care Medicine, Mie University Faculty and Graduate School of Medicine, Edobashi 2-174, Tsu, Mie, Japan. [email protected].
  • 26 Carl R. Woese Institute for Genomic Biology (Microbiome Metabolic Engineering), University of Illinois Urbana-Champaign, Urbana, IL, USA. [email protected].
  • 27 Department of Animal Science, University of Illinois Urbana-Champaign, Urbana, IL, USA. [email protected].
  • # Contributed equally.
PMID: 40855053 DOI: 10.1038/s41467-025-61847-2
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.

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