Plateau hypoxia induces pyroptosis in mouse kidney cells through NOD-like receptor signaling pathway
10.19405/j.cnki.issn1000-1492.2025.11.009
- VernacularTitle:高原低氧通过 NOD 样受体信号通路诱导小鼠肾脏细胞焦亡
- Author:
Xintong Xu
1
;
Xiaochen Chen
1
;
Chengling Cui
1
;
Xin Wang
1
;
Xiang Gao
1
Author Information
1. Dept of Basic Medicine , Qinghai University , Xining 810016
- Publication Type:Journal Article
- Keywords:
hypoxia;
kidney;
transcriptomics;
NOD-like receptor signaling pathway;
inflammatory factor;
pyroptosis
- From:
Acta Universitatis Medicinalis Anhui
2025;60(11):2052-2058
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the molecular mechanism of NOD-like receptor(NLR) signaling pathway induced cellular focal death in mouse kidney tissues under plateau hypoxia based on transcriptomic sequencing technology.
Methods:Animal models were constructed in high-altitude kidney test group(HKT group) and plain kidney control group(PKC group),and C57/BL6 mice were bred at an altitude of 4 200 m and 400 m,respectively.Kidney tissues were aseptically taken out after 30 d and used for observation of renal histopathological changes and transcriptomics sequencing,respectively,and then differentially expressed genes(DEGs) were enriched by KEGG and GO analysis.Key gene and protein expression levels were verified by reverse transcription quantitative polymerase chain reaction(RT-qPCR) and Western blot analysis.
Results:Hematoxylin-eosin(HE) staining showed that the renal tubules of HKT mice were disorganized,and the tubular epithelial cells were edematous with inflammatory cell aggregation.Transcriptomics sequencing analysis revealed that a total of 3 007 DEGs were identified in the HKT group,and KEGG analysis showed that DEGs were significantly enriched in the NLR signaling pathway.The mRNA expression of the key differentially expressed genes,CASP1,CASP11,GSDMD,IFI16,NAIP5,IRF9,and the downstream inflammatory factors,IL-1β and IL-18,was upregulated,and protein expression of CASP1,CASP11,and GSDMD was up-regulated.
Conclusion:The plateau hypoxic environment induces cellular pyroptosis by regulating the expression of NLR signaling pathway and releases downstream inflammatory factors to cause inflammatory responses.
- Full text:2026030510493249855高原低氧通过NOD样受体信号通路诱导小鼠肾脏细胞焦亡_许鑫桐.pdf
