ArticleReproductive sciences (Thousand Oaks, Calif.)2024
Fat Mass and Obesity-Associated Protein Regulates Granulosa Cell Aging by Targeting Matrix Metalloproteinase-2 Gene Via an N6-Methyladenosine-YT521-B Homology Domain Family Member 2-Dependent Pathway in Aged Mice.
Article in Reproductive sciences (Thousand Oaks, Calif.), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- RNA mJournal of advanced research · 2026Article
- Hydroxytyrosol Enhances the Nrf2/HO-1 Signalling Pathway to Inhibit Oxidative Stress and Apoptosis and Improve Premature Ovarian Insufficiency In Vitro and In Vivo.International journal of molecular sciences · 2026Article
- Unravelling Multilayered RNA Modification Networks in Female Reproduction and Obstetric/Gynaecologic Disorders.Biomolecules · 2026Review
- Critical roles of m6A demethylase FTO in ovarian aging.Biogerontology · 2026Review
- Epitranscriptomic regulation via m6A RNA modification in PCOS pathophysiology.Molecular biology reports · 2025Review
- The Clinical Relevance of FTO as a Demethylase Beyond Cancer: Molecular Mechanisms and Therapeutic Opportunities.Aging and disease · 2025Review
- Decreased FTO Expression Promotes Ovarian Granulosa Cells Aging.Reproductive sciences (Thousand Oaks, Calif.) · 2025Article
- Mechanical effects in aging of the musculoskeletal system: Molecular signaling and spatial scale alterations.Journal of orthopaedic translation · 2025Review
- Cellular senescence: from homeostasis to pathological implications and therapeutic strategies.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
In this study, we aimed to investigate the molecular mechanisms of RNA N6-methyladenosine (m6A) modification and how its associated proteins affect granulosa cell aging. A granulosa cell senescence model was constructed to detect the differences in total RNA m6A modification levels and the expression of related enzymes. Changes in downstream molecular expression and the effects on the cellular senescence phenotype were explored by repeatedly knocking down and overexpressing the key genes fat mass and obesity-associated protein (FTO), YT521-B homology domain family member 2 (YTHDF2), and matrix metalloproteinase-2 (MMP2). There was an increased total RNA m6A modification and decreased expression of the demethylase FTO and target gene MMP2 in senescent granulosa cells. FTO and MMP2 knockdown promoted granulosa cell senescence, whereas FTO and MMP2 overexpression retarded it. YTHDF2 and FTO can bind to the messenger RNA of MMP2. The extracellular signal-regulated kinase (ERK) pathway, which is downstream of MMP2, retarded the process of granulosa cell senescence through ERK activators. In granulosa cells, FTO can regulate the expression of MMP2 in an m6A-YTHDF2-dependent manner, influencing the activation status of the ERK pathway and contributing to the aging process of granulosa cells.
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