ArticleGastroenterology2018
Hedgehog-YAP Signaling Pathway Regulates Glutaminolysis to Control Activation of Hepatic Stellate Cells.
Article in Gastroenterology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 212 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
212 citing papers in PubMed, 319 citations in OpenAlex.
- Role of extracellular matrix in liver fibrosis regression and regeneration (Review).International journal of molecular medicine · 2026Review
- The circadian clock controls hepatic stellate cell activation via a BMAL1/CK1ε/REV-ERBα/transgelin signaling pathway.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Localization and Functional Analysis of theInsects · 2026Article
- Therapeutic Targets for Hepatic Fibrosis Driven by Hypoxia-Mediated Hepatic Stellate Cell Activation.Biomolecules · 2026Review
- Review
- Targeting YAP: mechanistic breakthroughs and therapeutic prospects in reversing organ fibrosis.Molecular and cellular biochemistry · 2026Review
- Sevoflurane ameliorates cerebral ischemia-reperfusion injury by modulating mitochondrial dynamics and attenuating apoptosis via Shh-YAP1 signaling pathway.Molecular brain · 2026Article
- Metabolomic and lipidomic plasma profiles according to metabolic dysfunction-associated steatotic liver diseases (MASLD) stages in the absence of type 2 diabetes (T2D).Metabolomics : Official journal of the Metabolomic Society · 2026Article
- Response to Kawamoto et al.EMBO reports · 2026Article
- Metabolic markers of kidney function and oxidative stress are associated with heart failure with preserved ejection fraction (HFpEF) in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD).Metabolomics : Official journal of the Metabolomic Society · 2026Article
- Mechanobiology of the Hippo-YAP Signaling Network.Cold Spring Harbor perspectives in biology · 2026Article
- Pirfenidone Sensitizes Hepatic Stellate Cells to Ferroptosis by Reprogramming Glutamine and Serine Metabolism for GSH Depletion.Antioxidants (Basel, Switzerland) · 2026Article
- YAP1 in control: how RNA networks and protein modifications shape its function and therapeutic targetability.Molecular cancer · 2026Review
- Liver Stiffness Rises Early in MASLD and Drives Inflammation, Lipid Dysmetabolism, and Fibrosis via Piezo1-YAP Mechanotransduction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Macrophage β-catenin-Ihh axis induces hepatic stellate cell activation and fibrosis in metabolic dysfunction-associated steatohepatitis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Decoding organ fibrosis: mechanistic insights and emerging therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- <p>Beyond hepatic stellate cell heterogeneity: Resolving fibrosis, restoring regeneration (Review)</p>.International journal of molecular medicine · 2026Review
- AMPK maintains the activation of hepatic stellate cells through mitophagy-induced metabolic reprogramming.Journal of molecular cell biology · 2026Article
- Effect of free fatty acids on TGF-β1 mediated fibrogenesis in hepatic stellate cells.Molecular metabolism · 2026Article
- Mechanical mechanics-reclaiming a new battlefield for chronic liver disease.Journal of advanced research · 2026Review
152 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsCirrhosis results from accumulation of myofibroblasts derived from quiescent hepatic stellate cells (Q-HSCs); it regresses when myofibroblastic HSCs are depleted. Hedgehog signaling promotes transdifferentiation of HSCs by activating Yes-associated protein 1 (YAP1 or YAP) and inducing aerobic glycolysis. However, increased aerobic glycolysis alone cannot meet the high metabolic demands of myofibroblastic HSCs. Determining the metabolic processes of these cells could lead to strategies to prevent progressive liver fibrosis, so we investigated whether glutaminolysis (conversion of glutamine to alpha-ketoglutarate) sustains energy metabolism and permits anabolism when Q-HSCs become myofibroblastic, and whether this is controlled by hedgehog signaling to YAP.
methodsPrimary HSCs were isolated from C57BL/6 or Smo
resultsExpression of genes that regulate glutaminolysis increased during transdifferentiation of primary Q-HSCs into myofibroblastic HSCs, and inhibition of glutaminolysis disrupted transdifferentiation. Blocking glutaminolysis in myofibroblastic HSCs suppressed mitochondrial respiration, cell growth and migration, and fibrogenesis; replenishing glutaminolysis metabolites to these cells restored these activities. Knockout of the hedgehog signaling intermediate smoothened or knockdown of YAP inhibited expression of glutaminase, the rate-limiting enzyme in glutaminolysis. Hedgehog and YAP inhibitors blocked glutaminolysis and suppressed myofibroblastic activities in HSCs. In livers of patients and of mice with acute or chronic fibrosis, glutaminolysis was induced in myofibroblastic HSCs. In mice with liver fibrosis, inhibition of glutaminase blocked accumulation of myofibroblasts and fibrosis progression.
conclusionsGlutaminolysis controls accumulation of myofibroblast HSCs in mice and might be a therapeutic target for cirrhosis.
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.