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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | 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 |
| Abstract | Background 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. Methods 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. Results 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. Conclusions 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. |
| Related Links | https://eurjmedres.biomedcentral.com/counter/pdf/10.1186/s40001-024-01742-6.pdf |
| Ending Page | 12 |
| Page Count | 12 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| DOI | 10.1186/s40001-024-01742-6 |
| Journal | European Journal of Medical Research |
| Issue Number | 1 |
| Volume Number | 29 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2024-03-01 |
| Access Restriction | Open |
| Subject Keyword | Medicine Public Health Infectious Diseases Internal Medicine Surgery Oncology Biomedicine TR4 Urosepsis Pyroptosis GSDMD Medicine/Public Health |
| Content Type | Text |
| Resource Type | Article |
| Subject | Medicine |
| Journal Impact Factor | 2.8/2023 |
| 5-Year Journal Impact Factor | 2.9/2023 |
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