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Trimethylamine Induced Chronic Kidney Injury by Activating the ZBP1-NLRP3 Inflammasome Pathway
1Department of Physiology, Hebei Medical University, Shijiazhuang, China. wuyum@yahoo.com; Hebei Provincial Hospital of Chinese Medicine, Hebei University of Chinese Medicine, Shijiazhuang, China. fhf701024@163.com.
Physiological Research
|November 15, 2024
Summary
Trimethylamine (TMA) causes kidney injury by activating the ZBP1-NLRP3 inflammasome pathway, not apoptosis or necroptosis. This finding reveals a novel mechanism in chronic kidney disease progression.
Area of Science:
- Biochemistry and Molecular Biology
- Nephrology and Urology
- Microbiology and Gut Microbiome
Background:
- Gut microbial metabolites like trimethylamine N-oxide (TMAO) are implicated in kidney disease pathogenesis.
- The specific role of trimethylamine (TMA) in chronic kidney injury and its associated programmed cell death (PCD) pathways remain uncharacterized.
Purpose of the Study:
- To investigate the contribution of TMA to chronic kidney injury.
- To identify the specific programmed cell death (PCD) pathway involved in TMA-induced kidney damage.
Main Methods:
- Male C57BL/6J mice were administered TMA intraperitoneally for three months.
- Kidney function was assessed by measuring plasma creatinine and blood urea nitrogen.
- Kidney tissue analysis included Masson staining for fibrosis and Western blotting for apoptosis, necroptosis, ferroptosis, and inflammasome markers (NLRP3, Caspase-1, IL-1beta, Caspase-8, ZBP1).
Main Results:
- TMA administration significantly elevated plasma creatinine and blood urea nitrogen, indicating impaired kidney function.
- Masson staining revealed increased fibrosis in TMA-treated mice compared to controls.
- TMA treatment upregulated key inflammasome components (NLRP3, Caspase-1, IL-1beta, Caspase-8, ZBP1) but did not affect markers of apoptosis, ferroptosis, or necroptosis.
Conclusions:
- Trimethylamine (TMA) induces chronic kidney injury and fibrosis in mice.
- The ZBP1-NLRP3 inflammasome pathway is critically involved in TMA-induced kidney damage.
- This study elucidates a novel mechanism linking gut microbial metabolites to kidney disease progression via inflammasome activation.
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