Trimethylamine N-oxide Induced Chronic Kidney Injury by Triggering PANoptosis.

Trimethylamine N-oxide (TMAO) is involved in the development of kidney disease. However, the specific mechanism by which it leads to kidney injury is unclear. This study explored the role of regulated cell death in TMAO-induced kidney injury. We constructed a TMAO-induced chronic kidney injury model...

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Publicado en:Physiological Research Vol. 74; no. 4; pp. 613 - 623
Autores principales: Decui SHAO, Lu BAI, Qian CHEN, Yuhong CHEN, Zhaoxu QIU, Yinuo LIU, Sheng JIN, Yuming WU, Jing DAI
Formato: Journal Article
Publicado: Institute of Physiology, Academy of Sciences of the Czech Republic Aug2025
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Aug2025
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      pub: Institute of Physiology, Academy of Sciences of the Czech Republic
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        atl: Trimethylamine N-oxide Induced Chronic Kidney Injury by Triggering PANoptosis.
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        au:
          Decui SHAO
          Lu BAI
          Qian CHEN
          Yuhong CHEN
          Zhaoxu QIU
          Yinuo LIU
          Sheng JIN
          Yuming WU
          Jing DAI
        affil: Laboratory of Cell Electrophysiology, Wannan Medical College, Anhui, China
      sug:
      ab: Trimethylamine N-oxide (TMAO) is involved in the development of kidney disease. However, the specific mechanism by which it leads to kidney injury is unclear. This study explored the role of regulated cell death in TMAO-induced kidney injury. We constructed a TMAO-induced chronic kidney injury model by intraperitoneal injection of TMAO (100 ìmol/kg/day for three months). Plasma creatinine (Cre) and urea nitrogen (BUN) levels were measured to evaluate kidney function. Masson staining was used to evaluate kidney pathological changes. The expression levels of regulated cell death-related proteins were measured using western blotting. Plasma Cre and BUN, the area of kidney fibrosis in the TMAO group significantly increased. The western blotting results showed cleaved-Caspase-8, Caspase-8, Caspase-1, NOD-like receptor protein 3 (NLRP3), interleukin-1#946; (IL-1#946;), cleaved-gasdermin D (cleaved-GSDMD), Z-DNA binding protein 1 (ZBP1), phosphorylation of receptor-interacting protein kinase 3 (RIP3) and mixed-lineage kinase domain-like pseudokinase (MLKL) significantly elevated in the TMAO group. The transferrin receptor 1 (TFR1), ferritin heavy chain (FTH), ferroportin (FPN), nuclear factor erythroid 2-related factor 2 (NRF2), and glutathione peroxidase 4 (GPX4) protein expression in kidney tissue of the TMAO group significantly up-regulated. However, there was no change in iron and MDA levels. The results suggested that PANoptosis, including pyroptosis, apoptosis, and necroptosis components, might be involved in TMAO-induced chronic kidney injury.
      pubtype: Academic Journal
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    language: English
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