ArticleScientific reports2017
TRAIL regulatory receptors constrain human hepatic stellate cell apoptosis.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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
16 citing papers in PubMed, 20 citations in OpenAlex.
- Therapeutic Potential of TLR8 Agonist GS-9688 (Selgantolimod) in Chronic Hepatitis B: Remodeling of Antiviral and Regulatory Mediators.Hepatology (Baltimore, Md.) · 2021Trial
- Pharmacological manipulation of liver fibrosis progression using novel HDAC6 inhibitors.The FEBS journal · 2025Article
- Role of PNPLA3 in Hepatic Stellate Cells and Hepatic Cellular Crosstalk.Liver international : official journal of the International Association for the Study of the Liver · 2025Review
- Time-course RNA sequencing reveals high similarity in mRNAome between hepatic stellate cells activated by agalactosyl IgG and TGF-β1.Functional & integrative genomics · 2024Article
- Apoptotic Receptors and CD107a Expression by NK Cells in an Interaction Model with Trophoblast Cells.Current issues in molecular biology · 2024Article
- Harnessing TRAIL-induced cell death for cancer therapy: a long walk with thrilling discoveries.Cell death and differentiation · 2023Review
- Tissue CD14Nature · 2023Article
- Synergistic anti-inflammatory effect of gut microbiota and lithocholic acid on liver fibrosis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022Article
- Endogenous TRAIL-R4 critically impacts apoptotic and non-apoptotic TRAIL-induced signaling in cancer cells.Frontiers in cell and developmental biology · 2022Article
- Hepatic Stellate Cell Activation and Inactivation in NASH-Fibrosis-Roles as Putative Treatment Targets?Biomedicines · 2021Review
- Immunity as Cornerstone of Non-Alcoholic Fatty Liver Disease: The Contribution of Oxidative Stress in the Disease Progression.International journal of molecular sciences · 2021Review
- Article
- Review
- Targeted Drug Delivery to Hepatic Stellate Cells for the Treatment of Liver Fibrosis.The Journal of pharmacology and experimental therapeutics · 2019Review
- TRAILblazing Strategies for Cancer Treatment.Cancers · 2019Review
- TRAIL-Dependent Resolution of Pulmonary Fibrosis.Mediators of inflammation · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
The TRAIL pathway can mediate apoptosis of hepatic stellate cells to promote the resolution of liver fibrosis. However, TRAIL has the capacity to bind to regulatory receptors in addition to death-inducing receptors; their differential roles in liver fibrosis have not been investigated. Here we have dissected the contribution of regulatory TRAIL receptors to apoptosis resistance in primary human hepatic stellate cells (hHSC). hHSC isolated from healthy margins of liver resections from different donors expressed variable levels of TRAIL-R2/3/4 (but negligible TRAIL-R1) ex vivo and after activation. The apoptotic potential of TRAIL-R2 on hHSC was confirmed by lentiviral-mediated knockdown. A functional inhibitory role for TRAIL-R3/4 was revealed by shRNA knockdown and mAb blockade, showing that these regulatory receptors limit apoptosis of hHSC in response to both oligomerised TRAIL and NK cells. A close inverse ex vivo correlation between hHSC TRAIL-R4 expression and susceptibility to apoptosis underscored its central regulatory role. Our data provide the first demonstration of non-redundant functional roles for the regulatory TRAIL receptors (TRAIL-R3/4) in a physiological setting. The potential for these inhibitory TRAIL receptors to protect hHSC from apoptosis opens new avenues for prognostic and therapeutic approaches to the management of liver fibrosis.
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.