ArticleNature communications2021
The methyltransferase METTL3 negatively regulates nonalcoholic steatohepatitis (NASH) progression.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 111 citations in OpenAlex.
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- The impactful role of the HDACs in the regulation of gene expression and as targets for disease therapy.Science advances · 2026Review
- N6-methyladenosine (m6A) methylation in adipose tissue: role, regulation, and therapeutic potential.Cellular and molecular life sciences : CMLS · 2026Review
- Chemokines and chemokine receptors in metabolic dysfunction-associated steatohepatitis: pathogenic mechanisms and clinical implications.Cellular & molecular biology letters · 2026Review
- METTL16 promotes MASLD progression through the regulation of lipid synthesis and immune response.Biology direct · 2026Article
- Cardiomyocyte Cyclin-dependent kinase 9 directly binds to and phosphorylates NF-κB p65 subunit to drive cardiac inflammation and remodeling.Nature communications · 2026Article
- Hepatocyte Mettl3 Deficiency Drives Primary Sclerosing Cholangitis and Liver Fibrosis via Cholangiocyte-Macrophage Crosstalk.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- NAT10 regulates heart development and function by maintaining the expression of genes related to fatty acid β-oxidation and heart contraction.Cell death and differentiation · 2026Article
- Unraveling the pleiotropic effects of CCR2-dependent signal transduction in fibrosis development.Theranostics · 2026Review
- A CD36-targeted aptamer-4-butyl-polyhydroxybenzophenone conjugate with pH-responsive release for liver delivery in MASLD.Regenerative biomaterials · 2026Article
- Histone lactylation: A key epigenetic modulator in the pathogenesis of metabolic dysfunction-associated steatohepatitis and alcoholic steatohepatitis.World journal of hepatology · 2025Review
- CD47 signaling in aging and age-related diseases: mechanisms, challenges, and therapeutic opportunities.Biogerontology · 2025Review
- The methyltransferase-like proteins as core regulators of nucleic acid modifications and post-translation modification of proteins in disease pathogenesis and therapeutic implications.Biomarker research · 2025Review
- Targeting RNA adenosine editing and modification enzymes for RNA therapeutics.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- YTHDC1 Is Essential for Postnatal Liver Development and Homeostasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- RNA Modifications in Health and Disease.MedComm · 2025Review
- Crotonylation of IDH1 alleviates MASLD progression by enhancing the TCA cycle.Nature communications · 2025Article
- METTL14-Induced MAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- METTL3: a multifunctional regulator in diseases.Molecular and cellular biochemistry · 2025Review
8 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nonalcoholic steatohepatitis (NASH) is a key step in the progression of nonalcoholic fatty liver (NAFL) to cirrhosis. However, the molecular mechanisms of the NAFL-to-NASH transition are largely unknown. Here, we identify methyltransferase like 3 (METTL3) as a key negative regulator of NASH pathogenesis. Hepatocyte-specific deletion of Mettl3 drives NAFL-to-NASH progression by increasing CD36-mediated hepatic free fatty acid uptake and CCL2-induced inflammation, which is due to increased chromatin accessibility in the promoter region of Cd36 and Ccl2. Antibody blockade of CD36 and CCL2 ameliorates NASH progression in hepatic Mettl3 knockout mice. Hepatic overexpression of Mettl3 protects against NASH progression by inhibiting the expression of CD36 and CCL2. Mechanistically, METTL3 directly binds to the promoters of the Cd36 and Ccl2 genes and recruits HDAC1/2 to induce deacetylation of H3K9 and H3K27 in their promoters, thus suppressing Cd36 and Ccl2 transcription. Furthermore, METTL3 is translocated from the nucleus to the cytosol in NASH, which is associated with CDK9-mediated phosphorylation of METTL3. Our data reveal a mechanism by which METTL3 negatively regulates hepatic Cd36 and Ccl2 gene transcription via a histone modification pathway for protection against NASH progression.
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