ArticleCell death discovery2023
Hepatic TNFRSF12A promotes bile acid-induced hepatocyte pyroptosis through NFκB/Caspase-1/GSDMD signaling in cholestasis.
Article in Cell death discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- A YAP-TEAD-CTCF Transcriptional Regulatory Axis Associated With the Elimination of Injured Hepatocytes From the Liver.Genes to cells : devoted to molecular & cellular mechanisms · 2026Article
- PPARα activation alleviates lithocholic acid-induced liver injury by inhibiting pyroptosis.Liver research (Beijing, China) · 2026Article
- NEDD8 Promotes the Progression and Inflammation of Keratoconus by Increasing the Expression of YAP1.Investigative ophthalmology & visual science · 2026Article
- Investigating the Role of TNFSF12 in Thyroid Cancer Progression via Single-Cell RNA Sequencing and Integrated Multiomics Analyses.Mediators of inflammation · 2026Article
- Over-Expression of TNFRSF12A Promotes Immune Suppression and Facilitates Angiogenesis in Triple-Negative Breast Cancer.Biology · 2025Article
- Conjugated bile acid-driven CD14JHEP reports : innovation in hepatology · 2025Article
- Chromatin dynamics and regulatory drivers of hypoplastic hepatic progenitor cells in partial hepatectomy model.Communications biology · 2025Article
- Article
- MetaQ: fast, scalable and accurate metacell inference via single-cell quantization.Nature communications · 2025Article
- Article
- Activation of pregnane X receptor protects against cholestatic liver injury by inhibiting hepatocyte pyroptosis.Acta pharmacologica Sinica · 2025Article
- TWEAK-Fn14: a promising target for cardio-cerebrovascular diseases and brain-heart syndrome.Frontiers in immunology · 2025Review
- Identifying novel therapeutic targets for non-alcoholic fatty liver disease using bioinformatics approaches: from drug repositioning to traditional Chinese medicine.Frontiers in bioinformatics · 2025Article
- Human vascularized macrophage-islet organoids to model immune-mediated pancreatic β cell pyroptosis upon viral infection.Cell stem cell · 2024Article
- Human Vascularized Macrophage-Islet Organoids to Model Immune-Mediated Pancreatic β cell Pyroptosis upon Viral Infection.bioRxiv : the preprint server for biology · 2024Article
- Unveiling the hidden dangers: a review of non-apoptotic programmed cell death in anesthetic-induced developmental neurotoxicity.Cell biology and toxicology · 2024Review
- AI-driven Discovery of Morphomolecular Signatures in Toxicology.bioRxiv : the preprint server for biology · 2024Article
- Analysis and experimental validation of IL-17 pathway and key genes as central roles associated with inflammation in hepatic ischemia-reperfusion injury.Scientific reports · 2024Article
- Integrating bulk and single-cell data to predict the prognosis and identify the immune landscape in HNSCC.Journal of cellular and molecular medicine · 2024Article
- Alendronate augments lipid A‑induced IL‑1β release by ASC‑deficient RAW264 cells via AP‑1 activation.Experimental and therapeutic medicine · 2023Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor necrosis factor receptor superfamily member-12A (TNFRSF12A) plays a critical role in inflammation and cell death. It is expressed in multiple tissues yet extremely low in normal liver. To date, little is known about its role in cholestasis. Therefore, we sought to delineate the role of TNFRSF12A in cholestasis and its underlying mechanisms. Human liver tissues were collected from patients with obstructive cholestasis (OC) or primary biliary cholangitis (PBC). Tnfrsf12a knockout (KO) mice were generated. Cholestasis was induced by bile-duct ligation (BDL) or 0.1% 5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-feeding. Human hepatoma PLC/PRF/5-ASBT and THP1 cell lines or primary mouse hepatocytes were used for mechanistic studies. Hepatic TNFRSF12A expression was markedly increased in OC or PBC patients. Genetic ablation of Tnfrsf12a in BDL- and 0.1%DDC-induced cholestatic mice significantly attenuated cholestatic liver injury with remarkable reduction of hepatocyte pyroptosis but without changing scores of necroptosis and apoptosis. Morphological features of hepatocyte pyroptosis and increased levels of pyroptosis-related proteins, NLRP3, cleaved-Caspase-1, and cleaved-GSDMD in OC patients and BDL-mice confirmed this observation. Further mechanistic studies revealed that bile acids (BAs) induced TNFRSF12A expression by enhancing the transcription factor c-JUN binding to the TNFRSF12A promoter and subsequently initiated hepatocyte pyroptosis by the NFκB/Caspase-1/GSDMD signaling. Interestingly, TWEAK, a typical ligand of TNFRSF12A, secreted by infiltrated macrophages in cholestatic livers, enhanced TNFRSF12A-induced hepatocyte pyroptosis. Taken together, we report, for the first time, that hepatic TNFRSF12A is dramatically increased in human cholestasis. Deletion of TNFRSF12A inhibits BAs-induced hepatocyte pyroptosis through the NFκB/Caspase-1/GSDMD signaling and thereby ameliorates cholestatic liver injury. As such, targeting TNFRSF12A could be a promising approach to treating cholestasis.
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.