ReviewRespiratory research2023
METTL3-mediated m6A RNA methylation induces the differentiation of lung resident mesenchymal stem cells into myofibroblasts via the miR-21/PTEN pathway.
Review in Respiratory research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
30 citing papers in PubMed, 36 citations in OpenAlex.
- METTL3 Promotes Lipid Deposition and Pulmonary Fibrosis by Destabilizing PLIN2 in a m6A-Dependent Manner.Journal of cellular and molecular medicine · 2026Article
- RNA Modifications as Molecular Regulators of Alveolar Epithelial Injury and Aberrant Repair in Pulmonary Fibrosis.Biomolecules · 2026Review
- [Molecular Mechanism of microRNA-429 TargetingSichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2026Article
- RNA Metabolism Genes as Prognostic Biomarkers and Therapeutic Targets in Colorectal Cancer Based on the Analysis of Single-Cell and Bulk-RNA Sequencing Data.Journal of cellular and molecular medicine · 2026Article
- Network medicine modeling of the m⁶A regulatory landscape identifies a KLF6-WTAP axis as a therapeutic target in pulmonary fibrosis.Journal of translational medicine · 2026Article
- Randomized Clinical Study of Laser-Assisted Delivery of Exosome Boosters for Postoperative Facial Scars and Facial Rejuvenation.Life (Basel, Switzerland) · 2026Article
- An hiPSC-derived multi-lineage lung model exhibiting proximal-distal epithelial features for modeling pulmonary fibrosis.Frontiers in cell and developmental biology · 2026Article
- The Emerging Role of METTL3 in Lung Diseases.International journal of molecular sciences · 2025Review
- MicroRNA chemical modifications in post-transcriptional gene silencing and human diseases.Molecular therapy. Nucleic acids · 2025Review
- Understanding the molecular basis of mesenchymal stem cell stemness: implications for clinical applications.Cell death & disease · 2025Review
- m6A Methylation-Modified hsa_circ_0044226 Attenuates Pulmonary Fibrosis by Suppressing Ferroptosis.Pulmonary circulation · 2025Article
- RNA 5-Methylcytosine Modification in Myocardial Fibrosis.Reviews in cardiovascular medicine · 2025Review
- Fibrotic Disease of the Skin and Lung: Shared Pathways, Environmental Drivers, and Therapeutic Opportunities in a Changing Climate.International journal of molecular sciences · 2025Review
- Mendelian randomization and single-cell analysis reveal causal relationships between renal clear cell carcinoma, kidney fibrosis, and inflammatory factors.Discover oncology · 2025Article
- The METTL3/TGF-β1 signaling axis promotes osteosarcoma progression by inducing MSC differentiation into CAFs via mJournal of bone oncology · 2025Article
- mInternational journal of molecular sciences · 2025Article
- Mechanisms and Therapeutic Potential of Myofibroblast Transformation in Pulmonary Fibrosis.Journal of respiratory biology and translational medicine · 2025Article
- Nitidine chloride inhibits the progression of hepatocellular carcinoma by suppressing IGF2BP3 and modulates metabolic pathways in an mMolecular medicine (Cambridge, Mass.) · 2025Article
- The role of epigenetics in pulmonary fibrosis: recent advances in mechanistic insights and therapeutic implications.Frontiers in molecular biosciences · 2025Review
- The impact of METTL3 on bladder cancer through mFrontiers in oncology · 2025Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe accumulation of myofibroblasts is the key pathological feature of pulmonary fibrosis (PF). Aberrant differentiation of lung-resident mesenchymal stem cells (LR-MSCs) has been identified as a critical source of myofibroblasts, but the molecular mechanisms underlying this process remain largely unknown. In recent years, N6-methyladenosine (m6A) RNA modification has been implicated in fibrosis development across diverse organs; however, its specific role in promoting the differentiation of LR-MSCs into myofibroblasts in PF is not well defined.
methodsIn this study, we examined the levels of m6A RNA methylation and the expression of its regulatory enzymes in both TGF-β1-treated LR-MSCs and fibrotic mouse lung tissues. The downstream target genes of m6A and their related pathways were identified according to a literature review, bioinformatic analysis and experimental verification. We also assessed the expression levels of myofibroblast markers in treated LR-MSCs and confirmed the involvement of the above-described pathway in the aberrant differentiation direction of LR-MSCs under TGF-β1 stimulation by overexpressing or knocking down key genes within the pathway.
resultsOur results revealed that METTL3-mediated m6A RNA methylation was significantly upregulated in both TGF-β1-treated LR-MSCs and fibrotic mouse lung tissues. This process directly led to the aberrant differentiation of LR-MSCs into myofibroblasts by targeting the miR-21/PTEN pathway. Moreover, inhibition of METTL3 or miR-21 and overexpression of PTEN could rescue this abnormal differentiation.
conclusionOur study demonstrated that m6A RNA methylation induced aberrant LR-MSC differentiation into myofibroblasts via the METTL3/miR-21/PTEN signaling pathway. We indicated a novel mechanism to promote PF progression. Targeting METTL3-mediated m6A RNA methylation and its downstream targets may present innovative therapeutic approaches for the prevention and treatment of PF.
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Registered trials
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.