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The Altered Proteomic Landscape in Renal Tubular Epithelial Cells under High Oxalate Stimulation
1Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Abstract:
Our study aimed to apply a proteomic approach to investigate the molecular mechanisms underlying the effects of oxalate on rat renal tubular epithelial cells. NRK-52E cells were treated with or without oxalate and subjected to quantitative proteomics to identify key proteins and key pathological changes under high oxalate stimulation. A total of 268 differentially expressed proteins (DEPs) between oxalate-treated and control groups were identified, with 132 up-regulated and 136 down-regulated proteins. Functional enrichment analysis revealed that DEPs are associated with oxidative stress, apoptosis, ferroptosis, pro-inflammatory cytokines, vitamin D, and biomineralization. SPP1, MFGE8, ANKS1A, and NAP1L1 were up-regulated in the oxalate-treated cells and the hyperoxaluric stone-forming rats, while SUB1, RNPS1, and DGLUCY were down-regulated in both cases. This altered proteomic landscape sheds light on the pathological processes involved in oxalate-induced renal damage and identifies potential biomarkers and therapeutic targets to mitigate the effects of hyperoxaluria and reduce the risk of CaOx stone formation.
Insights
This study used proteomics to find how oxalate affects kidney cells, identifying key proteins linked to kidney damage and calcium oxalate stone formation.
Area of Science:
- Proteomics
- Renal Cell Biology
- Biochemistry
Background:
- Hyperoxaluria is a major risk factor for calcium oxalate (CaOx) kidney stone formation.
- Understanding the molecular mechanisms of oxalate-induced renal tubular damage is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the molecular mechanisms of oxalate's effects on rat renal tubular epithelial cells using a proteomic approach.
- To identify key proteins and pathological changes associated with high oxalate stimulation.
- To discover potential biomarkers and therapeutic targets for hyperoxaluria and CaOx stone disease.
Main Methods:
- Quantitative proteomics was employed on NRK-52E cells treated with or without oxalate.
- Differentially expressed proteins (DEPs) were identified and quantified.
- Functional enrichment analysis was performed on identified DEPs.
Main Results:
- A total of 268 DEPs were identified, with 132 up-regulated and 136 down-regulated.
- DEPs were significantly associated with oxidative stress, apoptosis, ferroptosis, inflammation, vitamin D metabolism, and biomineralization.
- Specific proteins (SPP1, MFGE8, ANKS1A, NAP1L1) were up-regulated, while others (SUB1, RNPS1, DGLUCY) were down-regulated in both cell culture and hyperoxaluric rats.
Conclusions:
- The proteomic landscape alterations provide insights into oxalate-induced renal damage pathways.
- Identified proteins may serve as potential biomarkers for hyperoxaluria.
- The findings suggest novel therapeutic targets to mitigate oxalate nephrotoxicity and prevent CaOx stone formation.
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