ArticleGut2012
NKT-associated hedgehog and osteopontin drive fibrogenesis in non-alcoholic fatty liver disease.
Article in Gut, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 155 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
155 citing papers in PubMed, 265 citations in OpenAlex.
- When the Liver Flares: Inflammatory and Immunometabolic Mechanisms Driving the Transition from MASLD to MASH.Inflammation · 2026Review
- The Role of Kupffer Cells and Liver Macrophages in the Pathogenesis of Metabolic Dysfunction-Associated Steatotic Liver Disease.Biomedicines · 2026Review
- The immunometabolic nature of MASH: framing immune cells within metabolic dysfunction.Frontiers in immunology · 2026Review
- Interleukin-23 in lung and airway diseases: from pathogenesis to precision-guided therapeutic targeting.Frontiers in pharmacology · 2026Review
- Interleukin-18 binding protein protects against metabolic steatohepatitis.Hepatology communications · 2025Article
- Osteopontin: a central hub in the pathogenesis and therapeutic intervention of liver disease.Annals of medicine · 2025Review
- Dual roles of T cells in metabolic dysfunction-associated steatohepatitis pathogenesis and liver fibrosis: From inflammation to therapeutic targets.Hepatology communications · 2025Review
- ICOSL: more than a trigger of ICOS function.Cell communication and signaling : CCS · 2025Review
- MASH: the nexus of metabolism, inflammation, and fibrosis.The Journal of clinical investigation · 2025Review
- Review
- Hepatic iNKT cells facilitate colorectal cancer metastasis by inducing a fibrotic niche in the liver.iScience · 2025Article
- Osteopontin Promotes Cholangiocyte Secretion of Chemokines to Support Macrophage Recruitment and Fibrosis in MASH.Liver international : official journal of the International Association for the Study of the Liver · 2025Article
- Innate immune cells link dietary cues to normal and abnormal metabolic regulation.Nature immunology · 2025Review
- Invariant Natural Killer T lymphocytes as natural sensors for microbes: a two-edged sword in liver diseases.Frontiers in immunology · 2025Review
- Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): the interplay of gut microbiome, insulin resistance, and diabetes.Frontiers in medicine · 2025Review
- Osteopontin regulates right ventricular failure through integrin ανβ3/PERK/CHOP-dependent inflammatory and apoptotic pathways.Frontiers in immunology · 2025Article
- The microenvironment in the development of MASLD-MASH-HCC and associated therapeutic in MASH-HCC.Frontiers in immunology · 2025Review
- Osteokines in Nonalcoholic Fatty Liver Disease.Current obesity reports · 2024Review
- Hedgehog Signaling Pathway in Fibrosis and Targeted Therapies.Biomolecules · 2024Review
- The possible pathogenesis of liver fibrosis: therapeutic potential of natural polyphenols.Pharmacological reports : PR · 2024Review
95 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 5 institutions in 3 countries.
Funding
Abstract
objectiveImmune responses are important in dictating non-alcoholic steatohepatitis (NASH) outcome. We previously reported that upregulation of hedgehog (Hh) and osteopontin (OPN) occurs in NASH, that Hh-regulated accumulation of natural killer T (NKT) cells promotes hepatic stellate cell (HSC) activation, and that cirrhotic livers harbour large numbers of NKT cells.
designThe hypothesis that activated NKT cells drive fibrogenesis during NASH was evaluated by assessing if NKT depletion protects against NASH fibrosis; identifying the NKT-associated fibrogenic factors; and correlating plasma levels of the NKT cell-associated factor OPN with fibrosis severity in mice and humans.
resultsWhen fed methionine-choline-deficient (MCD) diets for 8 weeks, wild type (WT) mice exhibited Hh pathway activation, enhanced OPN expression, and NASH-fibrosis. Ja18-/- and CD1d-/- mice which lack NKT cells had significantly attenuated Hh and OPN expression and dramatically less fibrosis. Liver mononuclear cells (LMNCs) from MCD diet fed WT mice contained activated NKT cells, generated Hh and OPN, and stimulated HSCs to become myofibroblasts; neutralising these factors abrogated the fibrogenic actions of WT LMNCs. LMNCs from NKT-cell-deficient mice were deficient in fibrogenic factors, failing to activate collagen gene expression in HSCs. Human NASH livers with advanced fibrosis contained more OPN and Hh protein than those with early fibrosis. Plasma levels of OPN mirrored hepatic OPN expression and correlated with fibrosis severity.
conclusionHepatic NKT cells drive production of OPN and Hh ligands that promote fibrogenesis during NASH. Associated increases in plasma levels of OPN may provide a biomarker of NASH 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.