Abstract: SA-PO0152
Meis1 Targets Upb1 to Exacerbate AKI via 3-UPA-Mediated Impairment of Fatty Acid Metabolism
Session Information
- AKI: Mechanisms - 3
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Bai, Mi, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
- Zhang, Yue, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
- Jia, Zhanjun, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
- Zhang, Aihua, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
Background
Acute kidney injury (AKI) is a common clinical syndrome with high mortality. There are currently no effective therapies due to incomplete understanding on pathogenic mechanisms. Here, we elucidated the role and underlying mechanisms of Meis1 in AKI.
Methods
The AKI patients’ renal biopsy tissues, three AKI animal models (folic acid, ischemia/reperfusion injury and aristolochic acid), and renal tubular epithelial cells (TKPT) challenged with hypoxia/reoxygenation (H/R) were used to define the role of Meis1 in AKI, as well as the potential mechanisms.
Results
We observed the increased Meis1 expression in the nuclei of renal tubular epithelial cells of AKI patients (around 4 folds) and mice (around 3 folds). Proximal tubule-specific knock-in of Meis1 markedly exacerbated renal injury in the AKI models, evidenced by BUN (increased about 1.5 folds), Scr (increased about 1.7 folds), PAS staining, the expression of KIM-1 and NGAL at protein levels, and TUNEL staining, while administration of Meis1 inhibitors (MEISi) remarkably ameliorated folic acid- and ischemia-reperfusion-induced AKI. In vitro, overexpression of Meis1 aggravated H/R-induced cell death but alleviated by its inhibition. Using metabolomics analysis, luciferase reporter, ChIP assays, CUT & RUN and genomic manipulation, we further demonstrated that Meis1 transcriptionally repressed Upb1 expression, leading to the accumulation of 3-ureidopropionic acid (3-UPA), which significantly exacerbated tubular inflammation and cell death in vivo and in vitro. Finally, we performed omics analysis and a series of experiments and identified that the detrimental role of 3-UPA in AKI was possibly through its impairment on fatty acid metabolism in renal tubular epithelial cells.
Conclusion
Meis1/Upb1/3-UPA axis exerted a detrimental role in AKI, and targeting this axis (inhibiting Meis1 or activating Upb1) has therapeutic potential for AKI.
Funding
- Government Support – Non-U.S.