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Estimation of Urinary Nanocrystals in Humans using Calcium Fluorophore Labeling and Nanoparticle Tracking Analysis
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Dysregulated palmitic acid metabolism promotes the formation of renal calcium-oxalate stones through ferroptosis
Rui Wang1,2, Jingdong Zhang1, Haotian Ren1
1Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China.
Cellular and Molecular Life Sciences : CMLS
|February 12, 2024
Summary
Palmitic acid (PA) promotes kidney stone formation by inducing ferroptosis in renal cells through altered fatty acid metabolism. This finding offers new targets for treating calcium-oxalate stones.
Area of Science:
- Nephrology
- Metabolic pathways
- Cellular injury mechanisms
Background:
- Renal calcium-oxalate (CaOx) stone pathogenesis involves complex metabolic factors.
- Palmitic acid (PA) is an upregulated lipid metabolite in patients with CaOx stones.
Purpose of the Study:
- To mechanistically assess the role of PA in renal CaOx stone formation.
- To investigate the link between PA, fatty acid metabolism, and cellular processes in the kidney.
Main Methods:
- Lipidomics and transcriptomics analyses of PA-treated renal tubular epithelial cells.
- Investigated gene expression of desaturases (FADS1, FADS2), PPARα, and ferroptosis-related genes.
- Examined protein interactions involving PEBP1, 15-LO, and PKC ζ.
Main Results:
- PA induced desaturation and elongation of fatty acids, increasing polyunsaturated fatty acids (PUFAs).
- PA upregulated FADS1, FADS2, and PPARα, leading to PUFA formation and subsequent lipid peroxidation.
- PA promoted ferroptosis in renal cells via PUFA peroxides, phosphatidic acid metabolism, and PKC ζ activation, enhancing CaOx crystal adhesion.
Conclusions:
- PA promotes CaOx stone formation by inducing renal tubular epithelial cell ferroptosis.
- Dysregulated PUFA and phosphatidic acid metabolism driven by PA contributes to stone development.
- PA injures renal cells, promoting CaOx crystal deposition and offering potential therapeutic targets.
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