The interaction between C/EBPβ and TFAM promotes acute kidney injury via regulating NLRP3 inflammasome-mediated pyroptosis
| Autor: | Yuhang Ai, Qiong Li, Ze-Peng Duan, Zhenhua Zeng, Yu-Jing Wang, Tao Li, Yang Yang, Wei-Bo Huang, Xin-Gui Dai |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Lipopolysaccharides Male Inflammasomes Immunology Receptor for Advanced Glycation End Products Inflammation Cell Line Mitochondrial Proteins 03 medical and health sciences 0302 clinical medicine Adenosine Triphosphate NLR Family Pyrin Domain-Containing 3 Protein medicine Pyroptosis Animals Humans Secretion Promoter Regions Genetic Molecular Biology Gene knockdown Kidney Chemistry CCAAT-Enhancer-Binding Protein-beta Caspase 1 High Mobility Group Proteins Inflammasome TFAM Acute Kidney Injury Molecular biology DNA-Binding Proteins Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure medicine.symptom Signal transduction 030215 immunology medicine.drug Protein Binding Signal Transduction Transcription Factors |
| Zdroj: | Molecular immunology. 127 |
| ISSN: | 1872-9142 |
| Popis: | Sepsis-induced inflammatory damage is a crucial cause of acute kidney injury (AKI), and AKI is an ecumenical fearful complication in approximately half of patients with sepsis. CCAAT/enhancer-binding protein β (C/EBPβ) plays roles in regulating acute phase responses and inflammation. However, the role and mechanism of C/EBPβ in AKI are unclear. LPS combined with ATP-treated renal epithelial cells HK2 and cecal ligation-peferation (CLP)-mice were used as models of AKI in vitro and in vivo. Cell damage, the secretion of interleukin-1 beta (IL-1β), IL-18 and cysteinyl aspartate specific proteinase 1 (caspase-1) activity were tested by LDH, ELISA assay and flow cytometry analysis, respectively. The expression levels of TFAM, C/EBPβ, and pyroptosis-related molecules were tested by qRT-PCR and Western blotting. Chromatin immunoprecipitation (ChIP) assessed the interaction between C/EBPβ with TFAM. Hematoxylin-Eosin (H&E) staining detected pathological changes of kidney tissues, and immunohistochemistry measured TFAM and C/EBPβ in mice kidney tissues. C/EBPβ or TFAM were up-regulated in LPS combined with ATP -induced HK2 cells. Knockdown of C/EBPβ could suppress cell injury and the secretion of IL-1β and IL-18 induced by LPS combined with ATP. Furthermore, C/EBPβ up-regulated the expression levels of TFAM via directly binding to TFAM promoter. Overexpression of TFAM reversed the effects of C/EBPβ deficiency on pyroptosis. Knockdown of C/EBPβ could inhibit NLRP3 inflammasome-mediated caspase-1 signaling pathway by inactivating TFAM/RAGE pathway. It was further confirmed in the AKI mice that C/EBPβ and TFAM promoted AKI by activating NLRP3-mediated pyroptosis. The interaction of between C/EBPβ and TFAM facilitated pyroptosis by activating NLRP3/caspase-1 signal axis, thereby promoting the occurrence of AKI. |
| Databáze: | OpenAIRE |
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