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TR4 worsen urosepsis by regulating GSDMD.
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.
Afiliación
  • Wang H; Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, China.
  • Zhu S; Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, China.
  • Zhou Z; Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, China.
  • Wang Z; Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, China.
  • Zhuang W; Department of Urology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, China.
  • Xue D; Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, China.
  • Lu Z; Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, China.
  • Zheng Q; Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, China.
  • Ding L; Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, China.
  • Ren L; Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, China.
  • Luo W; Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, China.
  • Wang R; Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, China.
  • Ge G; Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, China.
  • Xia L; Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, China.
  • Li G; Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, China. 3193119@zju.edu.cn.
  • Wu H; Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, China. 3203015@zju.edu.cn.
Eur J Med Res ; 29(1): 151, 2024 Mar 01.
Article en En | MEDLINE | ID: mdl-38429762
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Líquidos Corporales / Sepsis Límite: Animals / Humans Idioma: En Revista: Eur J Med Res Asunto de la revista: MEDICINA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Líquidos Corporales / Sepsis Límite: Animals / Humans Idioma: En Revista: Eur J Med Res Asunto de la revista: MEDICINA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido