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Cell death‑related molecules and targets in the progression of urolithiasis (Review)
Liping Wu1, Xiaoyan Xue1, Chengwu He2
1Department of Pharmacy, Ganzhou People's Hospital, Ganzhou, Jiangxi 341099, P.R. China.
Abstract:
Urolithiasis is a high‑incidence disease caused by calcium oxalate (mainly), uric acid, calcium phosphate, struvite, apatite, cystine and other stones. The development of kidney stones is closely related to renal tubule cell damage and crystal adhesion and aggregation. Cell death, comprising the core steps of cell damage, can be classified into various types (i.e., apoptosis, ferroptosis, necroptosis and pyroptosis). Different crystal types, concentrations, morphologies and sizes cause tubular cell damage via the regulation of different forms of cell death. Oxidative stress caused by high oxalate or crystal concentrations is considered to be a precursor to a variety of types of cell death. In addition, complex crosstalk exists among numerous signaling pathways and their key molecules in various types of cell death. Urolithiasis is considered a metabolic disorder, and tricarboxylic acid cycle‑related molecules, such as citrate and succinate, are closely related to cell death and the inhibition of stone development. However, a literature review of the associations between kidney stone development, metabolism and various types of cell death is currently lacking, at least to the best of our knowledge. Thus, the present review summarizes the major advances in the understanding of regulated cell death and urolithiasis progression.
Insights
Kidney stone (urolithiasis) development involves renal tubule cell damage and various cell death types. Metabolism, particularly tricarboxylic acid cycle molecules, influences stone formation and cell death.
Area of Science:
- Nephrology
- Cell Biology
- Biochemistry
Background:
- Urolithiasis is a common condition driven by crystal formation, including calcium oxalate stones.
- Kidney stone pathogenesis is linked to renal tubule cell damage, crystal aggregation, and diverse cell death mechanisms like apoptosis, ferroptosis, necroptosis, and pyroptosis.
- Oxidative stress from high oxalate or crystal loads is a key factor initiating cell death pathways in urolithiasis.
Purpose of the Study:
- To review the current understanding of regulated cell death (RCD) in kidney stone (urolithiasis) progression.
- To explore the intricate relationship between metabolic disorders, specifically the tricarboxylic acid cycle, and cell death in the context of urolithiasis.
- To consolidate knowledge on how different crystal properties influence specific RCD pathways.
Main Methods:
- Comprehensive literature review of studies on urolithiasis, cell death, and metabolism.
- Analysis of signaling pathways and molecular crosstalk involved in various cell death types.
- Examination of the role of metabolic molecules like citrate and succinate in stone development and cell death inhibition.
Main Results:
- Different crystal types, concentrations, and morphologies induce distinct forms of tubular cell death.
- Oxidative stress is a significant precursor to multiple cell death modalities in urolithiasis.
- Metabolic factors, including tricarboxylic acid cycle intermediates, play a crucial role in modulating cell death and inhibiting stone formation.
Conclusions:
- Regulated cell death pathways are integral to kidney stone development and progression.
- Metabolic dysregulation is closely intertwined with cell death mechanisms in urolithiasis.
- Further research into the interplay between metabolism and RCD could reveal novel therapeutic strategies for urolithiasis.
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