ArticleHepatology (Baltimore, Md.)2010
Changes in the expression of methionine adenosyltransferase genes and S-adenosylmethionine homeostasis during hepatic stellate cell activation.
Article in Hepatology (Baltimore, Md.), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 58 citations in OpenAlex.
- Multi-Layer Omics Analysis Identifies Anxa3 and Coro1a as Candidate Targets of Pien Tze Huang in a Mouse Model of Liver Fibrosis.Biomedicines · 2026Article
- Extracellular Matrix Microstructures Modulate Hepatic Methionine Cycle and Methylations.Biomacromolecules · 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
- MAT2B regulates the protein level of MAT2A to preserve RNA N6-methyladenosine.Cell death & disease · 2024Article
- Single Nucleotide Polymorphisms ofGenes · 2022Article
- Review
- The Epigenetic Regulation of Microenvironment in Hepatocellular Carcinoma.Frontiers in oncology · 2021Review
- MAT2A-Mediated S-Adenosylmethionine Level in CD4Frontiers in immunology · 2021Article
- Methionine metabolism in chronic liver diseases: an update on molecular mechanism and therapeutic implication.Signal transduction and targeted therapy · 2020Review
- Mechanistic insights into the effects of SREBP1c on hepatic stellate cell and liver fibrosis.Journal of cellular and molecular medicine · 2020Article
- Homocysteine: A novel prognostic biomarker in liver transplantation for alpha-fetoprotein- negative hepatocellular carcinoma.Cancer biomarkers : section A of Disease markers · 2020Article
- MAT2B mediates invasion and metastasis by regulating EGFR signaling pathway in hepatocellular carcinoma.Clinical and experimental medicine · 2019Article
- Methionine adenosyltransferases in liver cancer.World journal of gastroenterology · 2019Review
- TGF-β1/p65/MAT2A pathway regulates liver fibrogenesis via intracellular SAM.EBioMedicine · 2019Article
- A paternal methyl donor-rich diet altered cognitive and neural functions in offspring mice.Molecular psychiatry · 2018Article
- Role of A-Kinase Anchoring Protein Phosphorylation in Alcohol-Induced Liver Injury and Hepatic Stellate Cell Activation.The American journal of pathology · 2018Article
- Deregulation of methionine metabolism as determinant of progression and prognosis of hepatocellular carcinoma.Translational gastroenterology and hepatology · 2018Review
- Methionine adenosyltransferases in liver health and diseases.Liver research (Beijing, China) · 2017Article
- Ubiquitin-Conjugating Enzyme 9 Phosphorylation as a Novel Mechanism for Potentiation of the Inflammatory Response.The American journal of pathology · 2016Article
- Role of methionine adenosyltransferase α2 and β phosphorylation and stabilization in human hepatic stellate cell trans-differentiation.Journal of cellular physiology · 2015Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
unlabelledHepatic stellate cell (HSC) activation is an essential event during liver fibrogenesis. Methionine adenosyltransferase (MAT) catalyzes biosynthesis of S-adenosylmethionine (SAMe), the principle methyl donor. SAMe metabolism generates two methylation inhibitors, methylthioadenosine (MTA) and S-adenosylhomocysteine (SAH). Liver cell proliferation is associated with induction of two nonliver-specific MATs: MAT2A, which encodes the catalytic subunit alpha2, and MAT2beta, which encodes a regulatory subunit beta that modulates the activity of the MAT2A-encoded isoenzyme MATII. We reported that MAT2A and MAT2beta genes are required for liver cancer cell growth that is induced by the profibrogenic factor leptin. Also, MAT2beta regulates leptin signaling. The strong association of MAT genes with proliferation and leptin signaling in liver cells led us to examine the role of these genes during HSC activation. MAT2A and MAT2beta are induced in culture-activated primary rat HSCs and HSCs from 10-day bile duct ligated (BDL) rat livers. HSC activation led to a decline in intracellular SAMe and MTA levels, a drop in the SAMe/SAH ratio, and global DNA hypomethylation. The decrease in SAMe levels was associated with lower MATII activity during activation. MAT2A silencing in primary HSCs and MAT2A or MAT2beta silencing in the human stellate cell line LX-2 resulted in decreased collagen and alpha-smooth muscle actin (alpha-SMA) expression and cell growth and increased apoptosis. MAT2A knockdown decreased intracellular SAMe levels in LX-2 cells. Activation of extracellular signal-regulated kinase and phosphatidylinositol-3-kinase signaling in LX-2 cells required the expression of MAT2beta but not that of MAT2A.
conclusionMAT2A and MAT2beta genes are induced during HSC activation and are essential for this process. The SAMe level falls, resulting in global DNA hypomethylation.
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