ArticleHepatology (Baltimore, Md.)2008
An inducible autocrine cascade regulates rat hepatocyte proliferation and apoptosis responses to tumor necrosis factor-alpha.
Article in Hepatology (Baltimore, Md.), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
38 citing papers in PubMed, 73 citations in OpenAlex.
- Immunology and treatments of fatty liver disease.Archives of toxicology · 2025Review
- A vascularized model of the human liver mimics regenerative responses.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Hepatic Natural Killer Cells: Organ-Specific Sentinels of Liver Immune Homeostasis and Physiopathology.Frontiers in immunology · 2019Review
- Administration of multipotent mesenchymal stromal cells restores liver regeneration and improves liver function in obese mice with hepatic steatosis after partial hepatectomy.Stem cell research & therapy · 2017Article
- Immunoregulatory Role of NK Cells in Tissue Inflammation and Regeneration.Frontiers in immunology · 2017Review
- Bioengineering considerations in liver regenerative medicine.Journal of biological engineering · 2017Review
- Mechanistic Modelling of Drug-Induced Liver Injury: Investigating the Role of Innate Immune Responses.Gene regulation and systems biology · 2017Article
- Cell biology is different in small volumes: endogenous signals shape phenotype of primary hepatocytes cultured in microfluidic channels.Scientific reports · 2016Article
- NKp46(+) natural killer cells attenuate metabolism-induced hepatic fibrosis by regulating macrophage activation in mice.Hepatology (Baltimore, Md.) · 2016Article
- Inhibition of sterile danger signals, uric acid and ATP, prevents inflammasome activation and protects from alcoholic steatohepatitis in mice.Journal of hepatology · 2015Article
- Metabolic danger signals, uric acid and ATP, mediate inflammatory cross-talk between hepatocytes and immune cells in alcoholic liver disease.Journal of leukocyte biology · 2015Article
- Using reconfigurable microfluidics to study the role of HGF in autocrine and paracrine signaling of hepatocytes.Integrative biology : quantitative biosciences from nano to macro · 2015Article
- Inflammasome activation and function in liver disease.Nature reviews. Gastroenterology & hepatology · 2015Review
- Dihydromyricetin alleviates carbon tetrachloride-induced acute liver injury via JNK-dependent mechanism in mice.World journal of gastroenterology · 2015Article
- Alcoholic liver disease: mechanisms of injury and targeted treatment.Nature reviews. Gastroenterology & hepatology · 2015Review
- Evolving concepts in the pathogenesis of NASH: beyond steatosis and inflammation.International journal of molecular sciences · 2014Review
- Co-regulation of primary mouse hepatocyte viability and function by oxygen and matrix.Biotechnology and bioengineering · 2014Article
- Primary hepatocytes and their cultures in liver apoptosis research.Archives of toxicology · 2014Review
- Models of signalling networks - what cell biologists can gain from them and give to them.Journal of cell science · 2013Review
- Modeling the intra- and extracellular cytokine signaling pathway under heat stroke in the liver.PloS one · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
unlabelledTumor necrosis factor-alpha (TNF) is an inflammatory cytokine that induces context-dependent proliferation, survival, and apoptosis responses in hepatocytes. TNF stimulates and enhances growth factor-mediated hepatocyte proliferation and survival following partial hepatectomy, but also acts in concert with other inflammatory cytokines of the innate immune response during viral infection to induce apoptosis in hepatocytes. In other epithelial cell types, TNF has recently been shown to stimulate autocrine release of transforming growth factor-alpha (TGF-alpha) and interleukin-1 (IL-1) family ligands. Here, we examine the role of these autocrine ligands in modulating TNF-induced proliferation and apoptosis in primary hepatocytes. We show that TNF-induced hepatocyte proliferation is regulated by an inducible, coupled, and self-antagonizing autocrine cascade involving the pro-proliferative TGF-alpha and IL-1 receptor antagonist (IL-1ra) ligands and antiproliferative IL-1alpha/beta ligands. Moreover, cooperative stimulation of hepatocyte proliferation by combined TNF and TGF-alpha treatment is self-limited through antiproliferative autocrine IL-1alpha/beta feedback. We show that TNF potently induces apoptosis of adenovirus-infected hepatocytes in a manner similarly determined through the integrated activity of a coupled TGF-alpha-IL-1alpha/beta-IL-1ra autocrine cascade. Exogenous TGF-alpha can either enhance or diminish apoptosis in adenoviral vector-treated and TNF-treated hepatocytes, in a biphasic relationship also mediated by autocrine IL-1alpha/beta feedback.
conclusionWe demonstrate that TNF-induced hepatocyte proliferation and apoptosis are both governed by a self-antagonizing TGF-alpha-IL-1alpha/beta-IL-1ra autocrine cascade in vitro, and thus identify multiple molecular targets for control of TNF-regulated hepatocyte phenotypic responses related to liver regeneration and adenoviral gene therapy.
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.