Background: Acute liver injury (ALI) is characterized by massive hepatocyte death and has high mortality and poor prognosis. Hepatocyte pyroptosis plays a key role in the pathophysiology of ALI and is involved in the inflammatory response mediated by NOD-like receptor protein 3 (NLRP3) inflammasome activation. Deltex 1 (DTX1) is a single transmembrane protein with ubiquitin E3 ligase activity and is closely involved in cell growth, differentiation, and apoptosis, as well as intracellular signal transduction. However, little is known about the influence of DTX1 on ALI. This study aimed to investigate the role of DTX1 in pyroptosis and inflammation induced by D-galactosamine (D-GalN) and tumor necrosis factoralpha (TNF-α) in human hepatocytes (LO2 cells) in vitro.
Methods: Cell pyroptosis was measured by flow cytometry. The levels of DTX1, pyroptosis-associated proteins, and inflammatory cytokines were detected by quantitative real-time polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay. Immunofluorescence staining, co-immunoprecipitation, ubiquitination, and luciferase reporter and chromatin immunoprecipitation assays were performed to detect the regulation between DTX1 and NLRP3 or hepatocyte nuclear factor 4 alpha (HNF4α). Analysis of variance was performed to compare groups.
Results: We found that DTX1 was decreased in D-GalN/TNF-α-induced LO2 cells. DTX1 overexpression significantly inhibited D-GalN/TNF-α-induced cell pyroptosis and inflammation. DTX1 interacted with NLRP3 and induced NLRP3 ubiquitination and degradation. Furthermore, by targeting NLRP3, DTX1 knockdown significantly induced cell pyroptosis and inflammation. In addition, HNF4α promoted DTX1 transcription by binding with its promoter.
Conclusion: Our study revealed that DTX1 suppressed D-GalN/TNF-α-induced hepatocyte pyroptosis and inflammation by regulating NLRP3 ubiquitination.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11417960 | PMC |
| http://dx.doi.org/10.1093/toxres/tfae145 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Anti-PD-1 exacerbates bleomycin-induced lung injury in mice via Caspase-3/GSDME-mediated pyroptosis.
Cell Death Dis
January 2025
State Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Department of Pulmonary and Critical Care Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, China.
Immune checkpoint inhibitors (ICIs) have significant therapeutic effects but can also cause fatal lung injury. However, the lack of mouse animal models of ICI-related lung injury (ICI-LI) has limited the in-depth exploration of its pathogenesis. In clinical practice, underlying lung diseases increase the risk of lung injury.
View Article and Find Full Text PDFNano Acacetin Mitigates Intestinal Mucosal Injury in Sepsis Rats by Protecting Mitochondrial Function and Regulating TRX1 to Inhibit the NLRP3 Pyroptosis Pathway.
Int J Nanomedicine
January 2025
Affiliated Hospital, Qinghai University, Xining, Qinghai, People's Republic of China.
Background: Acacetin (AC) is a flavonoid compound with antiperoxidant, anti-inflammatory, and antiplasmodial activity. However, the solubility of AC is poor and nano acacetin (Nano AC) was synthesized. The intestinal mucosal barrier is impaired in sepsis rats, and the protective effects and mechanism of AC and Nano AC on the intestinal mucosal barrier are unclear.
View Article and Find Full Text PDFThe Multifaceted Roles of Neutrophil Death in COPD and Lung Cancer.
J Respir Biol Transl Med
March 2025
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Chronic obstructive pulmonary disease (COPD) and lung cancer are closely linked, with individuals suffering from COPD at a significantly higher risk of developing lung cancer. The mechanisms driving this increased risk are multifaceted, involving genomic instability, immune dysregulation, and alterations in the lung environment. Neutrophils, the most abundant myeloid cells in human blood, have emerged as critical regulators of inflammation in both COPD and lung cancer.
View Article and Find Full Text PDFIdentification of immune characteristics of two lung adenocarcinoma subtypes based on immune- and pyroptosis-related genes to improve immunotherapy.
Bull Cancer
January 2025
Department of Respiratory and Critical Care Medicine, Baoji High-Tech Hospital, Baoji, 721000 Shaanxi, China. Electronic address:
Background: Lung adenocarcinoma (LUAD) is the most prevalent histological subtype of lung cancer. Pyroptosis is a programmatic cell death linked to inflammation.
Methods: The data information of 541 LUAD samples and 59 normal samples were obtained from TCGA database.
Network pharmacology, molecular docking, and experimental verification reveal the mechanism of Yi-Shen-Hua-Shi granules treating acute kidney injury.
J Ethnopharmacol
January 2025
Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No.197 Ruijin 2nd Road, Shanghai 200025, China. Electronic address:
Ethnopharmacological Relevance: Yi-Shen-Hua-Shi granules (YSHSG) have been shown to improve kidney function in various renal disorders, which are characterized by the sudden decline and impairment of kidney function.
Aim Of The Study: To investigate the precise mechanisms and targets of YSHSG in combating sepsis-induced AKI.
Materials And Methods: Through network pharmacology, the active ingredients, main target proteins, and related signaling pathways of YSHSG in the treatment of sepsis-induced AKI were predicted.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!