ArticleScience advances2024
Glycolysis in hepatic stellate cells coordinates fibrogenic extracellular vesicle release spatially to amplify liver fibrosis.
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Article in Science advances, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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27citing papers in PubMed
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Who cites it
27 citing papers in PubMed.
- With no lysine kinase 1 in hepatic stellate cells promotes mouse and human liver fibrosis through glycolytic triosephosphate isomerase 1.Hepatology (Baltimore, Md.) · 2026Article
- MASLD: Spatial Mechanisms and New Therapeutics.Biomolecules · 2026Review
- p21-activated kinase 4 drives hepatic stellate cell activation and liver fibrosis through the phosphorylation of YAP at T428.Signal transduction and targeted therapy · 2026Article
- Review
- Mechanisms and therapeutic insights into MASH-associated fibrosis.Trends in endocrinology and metabolism: TEM · 2026Review
- Macrophages expressing macrophage receptor with collagen structure attenuate liver fibrosis through a tissue restoration phenotype.JCI insight · 2026Article
- Decoding organ fibrosis: mechanistic insights and emerging therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- Lactylation in liver fibrosis: from molecular mechanisms to targeted therapeutic strategies.Frontiers in pharmacology · 2026Review
- Multidimensional regulation of hepatic macrophages in chronic liver disease: from metabolic reprogramming to intercellular and interorgan crosstalk.Frontiers in immunology · 2026Review
- Metabolic reprogramming in hepatic stellate cells: unveiling a novel therapeutic target for liver fibrosis.Frontiers in physiology · 2026Review
- Extracellular vesicles and acetylation: reciprocal regulation in disease progression.Frontiers in immunology · 2026Review
- Immunometabolic pathways in liver fibrosis: current evidence for selected plant-derived metabolites associated with traditional Chinese medicine.Frontiers in pharmacology · 2026Review
- Key Experimental Therapeutics and Knowledge Gaps in Metabolic Dysfunction-Associated Steatohepatitis (MASH).Drug design, development and therapy · 2026Review
- Hepatic Zonation in MASLD: Old Question, New Challenge in the Era of Spatial Omics.International journal of molecular sciences · 2025Review
- Causal pathways of plasma metabolites: unveiling metabolic associations in liver diseases.Nutrition & metabolism · 2025Article
- Glycolysis to lactylation: Unraveling the metabolic and epigenetic landscape in tissue fibrosis (Review).Molecular medicine reports · 2025Review
- Glycolytic Reprogramming in Uterine Fibroids: Genetic, Transcriptomic, Proteomic, and Metabolomic Insights.Genes · 2025Review
- Inflammation and immunity in liver homeostasis and disease: a nexus of hepatocytes, nonparenchymal cells and immune cells.Cellular & molecular immunology · 2025Review
- Reevaluating antiviral thresholds in HBV DNA-negative inactive HBsAg carriers: a multicenter histopathological analysis.Virology journal · 2025Article
- Extracellular Vesicles and Micro-RNAs in Liver Disease.Seminars in liver disease · 2025Review
Corrections and comments
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Authors and funding
27 authors.
Shalil KhanalDivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA.ORCID 0000-0002-5697-4061
Yuanhang LiuDepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, USA.
Adebowale O BamideleDivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA.ORCID 0000-0002-9547-2195
Alexander Q WixomDivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA.ORCID 0000-0003-2982-7303
Alexander M WashingtonBiochemistry and Molecular Biology Graduate Program, Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, MN 55905, USA.ORCID 0000-0002-9804-3329
Nidhi Jalan-SakrikarDivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA.ORCID 0000-0001-6795-0121
Shawna A CooperBiochemistry and Molecular Biology Graduate Program, Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, MN 55905, USA.ORCID 0000-0003-2669-7275
Ivan VuckovicMetabolomics Core, Mayo Clinic, Rochester, MN 55905, USA.ORCID 0000-0001-7806-7238
Song ZhangDepartment of Cardiovascular Medicine, Mayo Clinic, Rochester, MN 55905, USA.ORCID 0000-0002-9786-802X
Jun ZhongDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA.ORCID 0000-0003-3148-4143
Kenneth L JohnsonProteomics Core, Mayo Clinic, Rochester, MN 55905, USA.ORCID 0000-0002-8267-8047
M Cristine CharlesworthProteomics Core, Mayo Clinic, Rochester, MN 55905, USA.
Iljung KimDepartment of Computer Science, Hanyang University, Seoul 04763, Republic of South Korea.ORCID 0009-0000-7924-1293
Yubin YeonDepartment of Computer Science, Hanyang University, Seoul 04763, Republic of South Korea.ORCID 0009-0005-7771-9050
Sangwoong YoonSchool of Computational Sciences, Korea Institute for Advanced Study, Seoul 02455, Republic of South Korea.ORCID 0000-0002-7251-3230
Yung-Kyun NohDepartment of Computer Science, Hanyang University, Seoul 04763, Republic of South Korea.ORCID 0000-0002-6372-9267
Chady MerouehDepartment of Pathology, Division of Anatomic Pathology, Mayo Clinic, Rochester, MN 55905, USA.ORCID 0000-0003-2352-4336
Abdul Aziz TimbillaDivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA.ORCID 0009-0004-5960-0374
Usman YaqoobDivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA.
Jinhang GaoDivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA.ORCID 0000-0003-0480-7867
Yohan KimDepartment of Urology, Mayo Clinic, Rochester, MN 55905, USA.ORCID 0000-0002-2378-0068
Fabrice LucienDepartment of Urology, Mayo Clinic, Rochester, MN 55905, USA.ORCID 0000-0001-6149-345X
Robert C HuebertDivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA.
Nissim HayDepartment of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, IL 60607, USA.
Michael SimonsCardiovascular Research Center, Yale University, New Haven, CI 06510, USA.ORCID 0000-0003-0348-7734
Vijay H ShahDivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA.ORCID 0000-0001-7620-573X
Enis KostallariDivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA.ORCID 0000-0002-7138-5580
Funding
Women's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI Felicity Enders · 1985 to 2026
$151.3MPILOT AND FEASIBILTY PROGRAMP30DK084567 · NIDDK · MAYO CLINIC ROCHESTER · PI GREGORY J. GORES · 2009 to 2026
$22.2MInstitutional Career Development CoreKL2TR002379 · NCATS · MAYO CLINIC ROCHESTER · PI NILUFER ERTEKIN-TANER · 2017 to 2026
$14.9MMolecular Mechanisms of Liver Fibrosis (Diversity Supplement)R37AA021171 · NIAAA · MAYO CLINIC ROCHESTER · PI VIJAY H. SHAH · 2019 to 2026
$3.0MMolecular Mechanisms of Cholestatic FibrogenesisR01DK117861 · NIDDK · MAYO CLINIC ROCHESTER · PI Robert Christian Huebert · 2019 to 2026
$2.8MMolecular Mechanisms of Liver FibrosisR01AA021171 · NIAAA · MAYO CLINIC ROCHESTER · PI SHAH, VIJAY H. · 2012 to 2018
$2.5MPathobiology of liver fibrosisR01DK136511 · NIDDK · MAYO CLINIC ROCHESTER · PI Enis Kostallari · 2023 to 2026
$1.4MNIDDK Multidisciplinary Predoctoral Training in Discovery and Translational ResearchT32DK124190 · NIDDK · MAYO CLINIC ROCHESTER · PI DANIEL D BILLADEAU, MARK A. MC NIVEN · 2020 to 2026
$1.3MGastrointestinal Cues Influence Metabolic Control of Regulatory T cell FunctionK01DK124358 · NIDDK · MAYO CLINIC ROCHESTER · PI BAMIDELE, ADEBOWALE O · 2020 to 2024
$723kNCATS NIH HHS KL2 TR002379NCI NIH HHS P30 CA015083NIAAA NIH HHS R01 AA021171NIAAA NIH HHS R37 AA021171NIDDK NIH HHS K01 DK124358NIDDK NIH HHS P30 DK084567NIDDK NIH HHS R01 DK117861NIDDK NIH HHS R01 DK136511NIDDK NIH HHS T32 DK124190
Abstract
Liver fibrosis is characterized by the activation of perivascular hepatic stellate cells (HSCs), the release of fibrogenic nanosized extracellular vesicles (EVs), and increased HSC glycolysis. Nevertheless, how glycolysis in HSCs coordinates fibrosis amplification through tissue zone-specific pathways remains elusive. Here, we demonstrate that HSC-specific genetic inhibition of glycolysis reduced liver fibrosis. Moreover, spatial transcriptomics revealed a fibrosis-mediated up-regulation of EV-related pathways in the liver pericentral zone, which was abrogated by glycolysis genetic inhibition. Mechanistically, glycolysis in HSCs up-regulated the expression of EV-related genes such as Ras-related protein Rab-31 (
Indexed as
Extracellular VesiclesGlycolysisHepatic Stellate CellsLiver CirrhosisAnimalsDisease Models, AnimalHumansLiverMaleMiceMice, Inbred C57BLrab GTP-Binding Proteinsrab GTP-Binding Proteins
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Read underepoch 390
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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.