ArticleThe American journal of pathology2020
Pyruvate Kinase M2 Tetramerization Protects against Hepatic Stellate Cell Activation and Liver Fibrosis.
Article in The American journal of pathology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 78 citations in OpenAlex.
- circCACNA1D drives pulmonary fibrosis by regulating pyruvate kinase M2 dimer‑tetramer switching.International journal of molecular medicine · 2026Article
- Metabolic reprogramming in fibrosis-related diseases: underlying mechanisms and therapeutics.Molecular biomedicine · 2026Review
- Metabolic Pathways Linking Atherosclerotic Cardiovascular Disease With Metabolic Dysfunction-Associated Steatotic Liver Disease.Current atherosclerosis reports · 2026Review
- HBV-Induced Pyruvate Increases Lactylation of Pyruvate Kinase M2 (PKM2) at K206 to Promote Liver Fibrosis.Pathogens (Basel, Switzerland) · 2026Article
- H3K9 acetylation-dependent CHAC1 transcription in dihydroartemisinin-induced hepatic stellate cell ferroptosis.Chinese medical journal · 2026Article
- Biliary atresia-related liver fibrosis.Frontiers in cell and developmental biology · 2026Review
- Succinylation: novel molecular mechanisms and prospects for targeted therapy in liver diseases.Frontiers in molecular biosciences · 2026Review
- Metabolic reprogramming in hepatic stellate cells: unveiling a novel therapeutic target for liver fibrosis.Frontiers in physiology · 2026Review
- PKM2 mediates the glycolytic response to matrix stiffness in lung fibroblasts.Frontiers in cell and developmental biology · 2026Article
- Pyruvate kinase M2 is elevated in systemic sclerosis and plays a role in its pathogenesis.Frontiers in immunology · 2026Article
- Impact ofPlants (Basel, Switzerland) · 2025Article
- Loss of Dioxin Response Element-Mediated Induction of PKM2 Reprograms Hepatic Metabolism in Response to TCDD.International journal of molecular sciences · 2025Article
- Glycolysis to lactylation: Unraveling the metabolic and epigenetic landscape in tissue fibrosis (Review).Molecular medicine reports · 2025Review
- Recent progress in the development of small molecule pyruvate kinase M2 inhibitors: 2020-2025.Future medicinal chemistry · 2025Review
- Regulation of Hepatic Stellate Cell Phenotypes in Metabolic Dysfunction-Associated Steatohepatitis.Gastroenterology · 2025Review
- Pyruvate Kinase M2 Links Metabolism and Epigenetics: A New Target for Liver Disease Treatment.Biomolecules · 2025Review
- Pyruvate kinase M2 modulates Japanese encephalitis virus replication in neuronal cells.The Journal of general virology · 2025Article
- Role of immune cell subsets in liver fibrosis through single-cell RNA sequencing and array.Cancer biomarkers : section A of Disease markers · 2025Article
- Metabolic Sparks in the Liver: Metabolic and Epigenetic Reprogramming in Hepatic Stellate Cells Activation and Its Implications for Human Metabolic Diseases.Diabetes & metabolism journal · 2025Review
- Inhibition of colorectal cancer cell growth by downregulation of M2-PK and reduction of aerobic glycolysis by clove active ingredients.Frontiers in pharmacology · 2025Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
Liver fibrosis is an increasing health problem worldwide, for which no effective antifibrosis drugs are available. Although the involvement of aerobic glycolysis in hepatic stellate cell (HSC) activation has been reported, the role of pyruvate kinase M2 (PKM2) in liver fibrogenesis still remains unknown. We examined PKM2 expression and location in liver tissues and primary hepatic cells. The in vitro and in vivo effects of a PKM2 antagonist (shikonin) and its allosteric agent (TEPP-46) on liver fibrosis were investigated in HSCs and liver fibrosis mouse model. Chromatin immunoprecipitation sequencing and immunoprecipitation were performed to identify the relevant molecular mechanisms. PKM2 expression was significantly up-regulated in both mouse and human fibrotic livers compared with normal livers, and mainly detected in activated, rather than quiescent, HSCs. PKM2 knockdown markedly inhibited the activation and proliferation of HSCs in vitro. Interestingly, the PKM2 dimer, rather than the tetramer, induced HSC activation. PKM2 tetramerization induced by TEPP-46 effectively inhibited HSC activation, reduced aerobic glycolysis, and decreased MYC and CCND1 expression via regulating histone H3K9 acetylation in activated HSCs. TEPP-46 and shikonin dramatically attenuated liver fibrosis in vivo. Our findings demonstrate a nonmetabolic role of PKM2 in liver fibrosis. PKM2 tetramerization or suppression could prevent HSC activation and protects against liver fibrosis.
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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.