TR4 worsen urosepsis by regulating GSDMD

• Published in: European journal of medical research 2024-03, Vol.29 (1), p.151-151, Article 151
• Main Authors: Wang, Huan, Zhu, Shibin, Zhou, Zhenwei, Wang, Zhenghui, Zhuang, Wei, Xue, Dingwei, Lu, Zeyi, Zheng, Qiming, Ding, Lifeng, Ren, Liangliang, Luo, Wenqing, Wang, Ruyue, Ge, Guangju, Xia, Liqun, Li, Gonghui, Wu, Haiyang
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Bacteria; Body Fluids; Chromatin; Cytokine storm; Cytokines; E coli; Eosine Yellowish-(YS); Escherichia coli; Gasdermins; GSDMD; Health aspects; Humans; Immune response; Infection; Infections; Macrophages; Medical research; Medicine, Experimental; Membranes; Mice; Mortality; Multiple organ dysfunction syndrome; Online databases; Phosphate-Binding Proteins - genetics; Plasmids; Proteins; Pyroptosis; Scientific equipment and supplies industry; Sepsis; Sepsis - complications; Sepsis - genetics; TR4; Transgenic animals; Tumor necrosis factor-TNF; Urosepsis
• ISSN: 2047-783X; 0949-2321; 2047-783X
• DOI: 10.1186/s40001-024-01742-6

Urosepsis is a life-threatening organ disease in which pathogenic microorganisms in the urine enter the blood through the vessels, causing an imbalance in the immune response to infection. The aim of this study was to elucidate the role of testicular orphan receptor 4 (TR4) in urosepsis. The role of TR4 in the progression and prognosis of urosepsis was confirmed by analyzing data from online databases and clinical human samples. To mimic urosepsis, we injected E. coli bacteria into the renal pelvis of mice to create a urosepsis model. Hematoxylin and eosin staining was used to observe histopathological changes in urosepsis. The effects of the upregulation or downregulation of TR4 on macrophage pyroptosis were verified in vitro. Chromatin immunoprecipitation assay was used to verify the effect of TR4 on Gasdermin D (GSDMD) transcription. TR4 was more highly expressed in the nonsurviving group than in the surviving group. Furthermore, overexpressing TR4 promoted inflammatory cytokine expression, and knocking down TR4 attenuated inflammatory cytokine expression. Mechanistically, TR4 promoted pyroptosis by regulating the expression of GSDMD in urosepsis. Furthermore, we also found that TR4 knockdown protected mice from urosepsis induced by the E. coli. TR4 functions as a key regulator of urosepsis by mediating pyroptosis, which regulates GSDMD expression. Targeting TR4 may be a potential strategy for urosepsis treatment.