Abstract: SA-PO143
Spatially Resolved Metabolomics to Discover Metabolic Alterations in PHF14-Associated Kidney Protection after Acute Kidney Injury
Session Information
- AKI: Metabolism and Cell Death
October 26, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Chen, Jiaxin, Shanghai Changzheng Hospital, Shanghai, Shanghai, China
- Xue, Cheng, Shanghai Changzheng Hospital, Shanghai, Shanghai, China
- Mao, Zhiguo, Shanghai Changzheng Hospital, Shanghai, Shanghai, China
Background
Acute kidney injury (AKI) is a severe clinical syndrome，and a considerable part of AKI patients underwent maladaptive repair, resulting in renal fibrosis and chronic kidney disease. The epigenetic regulatory plant homologous domain Zinc finger protein-14 (PHF14) was proved to play a key role in inhibiting renal fibrosis after AKI, and its specific mechanism needs to be further clarified. This study aims to explore the mechanism of PHF14 inhibiting maladaptive repair after AKI from the metabolic level, so as to discover new therapeutic targets.
Methods
In this study, wild type (WT) and PHF14 knockout (PHF14-/-) mice were treated with folic acid (FA) to induce acute kidney injury. The renal function and histopathological were detected. Air-flow-assisted desorption electrospray ionization (AFADESI) was employed for metabolite analysis in cortical and medulla areas of mice kidney. Then the differential metabolites (DEMs) were identified respectively and KEGG enrichment was performed to identify the metabolic changes, and the DEMs were selected for mass spectrometry imaging analysis to determine their spatial distribution in the kidney.
Results
After 14 days of folic acid induction, renal function decreased, obvious inflammatory cell infiltration and fibrosis in kidney interstitial; while in PHF14-/- mice, were more serious. Compared with WT, different metabolites in the renal cortex and medulla of WT and PHF14-/- mice treated with FA were mainly concentrated in lipid metabolism, polyamine biosynthesis and TCA cycle, metabolites such as carnitine, glycerophospholipids, fatty acids, arginine, spermidine, succinic acid, malic acid and L-aspartic acid had significant changes in the kidney.
Conclusion
Spatial metabolomics was applied to investigate the changes of renal tissue metabolism after AKI, and the finding revealed the effect of PHF14 on renal metabolism after AKI, which proposed potential targets for the prevention and treatment of AKI.
Distribution of Polyamine metabolites.
Funding
- Clinical Revenue Support