ArticleClinical and translational medicine2023
Genetic and pharmacological inhibition of METTL3 alleviates renal fibrosis by reducing EVL m6A modification through an IGF2BP2-dependent mechanism.
Article in Clinical and translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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36 citing papers in PubMed, 45 citations in OpenAlex.
- RNA mActa pharmacologica Sinica · 2026Review
- Pharmacological targeting of kidney fibrosis: druggable mechanisms, translational models, and emerging antifibrotic therapies.Clinical kidney journal · 2026Review
- RNA modifications in organ fibrosis: bibliometric evolution, convergent mechanisms, and emerging pharmacological targets.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Epigenetic orchestration of scar formation: Therapeutic potential of targeting DNA methylation and non‑coding RNAs in cutaneous fibrosis (Review).Molecular medicine reports · 2026Review
- Epitranscriptomics in kidney disease: insights and therapeutic potential.Kidney research and clinical practice · 2026Article
- The m5C orchestrator NSUN7 drives SPARC/HMGB1 axis-mediated inflammation to exacerbate kidney injury.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Haikun Shenxi Capsule Alleviates Renal Fibrosis in CKD Mice by Targeting the METTL3/IGF2BP3-Mediated m6A Modification of NKD2.Mediators of inflammation · 2026Article
- METTL14-mediated mEpigenetics · 2025Article
- Emerging epigenetic modifications in renal fibrosis: From mechanisms to treatments.Acta pharmaceutica Sinica. B · 2025Review
- METTL14 Regulates the Expression of Genes Related to Interferon, Interleukin and MHC Class I in Nasopharyngeal Carcinoma Cells.Cancer medicine · 2025Article
- IGF2BP3 regulates EMP1 stability in an mCell death & disease · 2025Article
- mScience China. Life sciences · 2025Article
- Targeting RNA adenosine editing and modification enzymes for RNA therapeutics.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- METTL3/YTHDF3 mJournal of diabetes investigation · 2025Article
- Renal tubular epithelial IGFBP7 interacts with PKM2 to drive renal lipid accumulation and fibrosis.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Decoding mJournal of translational medicine · 2025Review
- ALKBH5 regulates intrauterine adhesion progression through m6A dependent FABP4 mRNA stabilization and serum lipid metabolism.Communications biology · 2025Article
- METTL3 promotes the hypertrophic scar fibrosis via m6A RNA methylation of GRAMD1B mRNA.Journal of molecular histology · 2025Article
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13 authors at 2 institutions in 2 countries.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundN
methodsRenal tissues from humans and mice as well as HK-2 cells were used as research subjects. The profiles of m6A modification and regulators in renal fibrosis were analysed at the protein and RNA levels using Western blotting, quantitative real-time polymerase chain reaction and other methods. Methylation RNA immunoprecipitation sequencing and RNA sequencing coupled with methyltransferase-like 3 (METTL3) conditional knockout were used to explore the function of METTL3 and potential targets. Gene silencing and overexpression combined with RNA immunoprecipitation were performed to investigate the underlying mechanism by which METTL3 regulates the Ena/VASP-like (EVL) m6A modification that promotes renal fibrosis. Molecular docking and virtual screening with in vitro and in vivo experiments were applied to screen promising traditional Chinese medicine (TCM) monomers and explore their mechanism of regulating the METTL3/EVL m6A axis and anti-renal fibrosis.
resultsMETTL3 and m6A modifications were hyperactivated in both the tubular region of fibrotic kidneys and HK-2 cells. Upregulated METTL3 enhanced the m6A modification of EVL mRNA to improve its stability and expression in an insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2)-dependent manner. Highly expressed EVL binding to Smad7 abrogated the Smad7-induced suppression of transforming growth factor-β (TGF-β1)/Smad3 signal transduction, which conversely facilitated renal fibrosis progression. Molecular docking and virtual screening based on the structure of METTL3 identified a TCM monomer named isoforsythiaside, which inhibited METTL3 activity together with the METTL3/EVL m6A axis to exert anti-renal fibrosis effects.
conclusionsCollectively, the overactivated METTL3/EVL m6A axis is a potential target for renal fibrosis therapy, and the pharmacological inhibition of METTL3 activity by isoforsythiaside suggests that it is a promising anti-renal fibrosis agent.
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