Microbiota-derived corisin accelerates kidney fibrosis by promoting cellular aging
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.
Authors
- Yutaka Yano (ORCID: https://orcid.org/0000-0003-0234-1207)
- Isaac Cann (ORCID: https://orcid.org/0000-0003-0539-0119)
- Atsuro Takeshita
- Atsushi Tomaru
- Chisa Inoue (ORCID: https://orcid.org/0000-0002-7022-9156)
- Hajime Fujimoto (ORCID: https://orcid.org/0000-0003-2440-9655)
- Diwakar Shukla (ORCID: https://orcid.org/0000-0003-4079-5381)
- Xuenan Mi (ORCID: https://orcid.org/0009-0001-5237-4712)
- Taro Yasuma
- Esteban C. Gabazza (ORCID: https://orcid.org/0000-0001-5748-1499)
- Tetsu Kobayashi (ORCID: https://orcid.org/0000-0003-4397-6137)
- Roderick Ian Mackie (ORCID: https://orcid.org/0000-0002-4767-9300)
- Kota Nishihama (ORCID: https://orcid.org/0000-0002-0471-5164)
- Mei Uemura
- Tetsuya Nosaka (ORCID: https://orcid.org/0000-0002-0037-7049)
- Corina N. D’Alessandro‐Gabazza (ORCID: https://orcid.org/0000-0003-2164-5775)
- Justine Arrington (ORCID: https://orcid.org/0000-0003-1511-8805)
- Ahmed M. Abdel-Hamid (ORCID: https://orcid.org/0000-0002-4557-2008)
- Kyle R. Leistikow (ORCID: https://orcid.org/0000-0002-7719-4179)
- Yuko Okano
- Manal A. B. Alhawsawi
- Hidetoshi Yamazaki
- Christopher J. Fields (ORCID: https://orcid.org/0000-0002-7749-5844)
- Ryoichi Ono
- Masaaki Toda
- Tomohito Okano
- Osamu Hataji
- Valeria Fridman D’Alessandro
- Michael R. King
- Tomoko Anoh
Institutions
- University of Illinois Urbana-Champaign (US)
- Mie University (JP)
- Urbana University (US)
- Ecologie microbienne (FR)
- Soka Municipal Hospital (JP)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-08-25
- DOI
- https://doi.org/10.1038/s41467-025-61847-2
- Citations
- 1
- Primary Topic
- Chronic Kidney Disease and Diabetes
- Type
- article
- Field-Weighted Citation Impact
- 1.43
Funders
- Eli Lilly and Company
- Takeda Science Foundation
- Japan Association for Diabetes Education and Care
- Japan Society of Nutrition and Food Science
- Eli Lilly Japan
- Japan Society for the Promotion of Science
- Japan Science and Technology Agency