ArticleProceedings of the National Academy of Sciences of the United States of America2021
FGF-2-dependent signaling activated in aged human skeletal muscle promotes intramuscular adipogenesis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 62 citations in OpenAlex.
- Effects of the Foam Massage Roller on VEGF-A and FGF-2 Blood Levels in Young Men.In vivo (Athens, Greece)Trial
- State-Dependent FGF Signaling in Satellite Cell-Mediated Skeletal Muscle Regeneration and Pathological Remodeling.Biomolecules · 2026Review
- Moderate Intensity Exercise Training in Combination with L-Carnitine Ameliorates The Varicocele-Suppressed Self-Renewal; Implication onInternational journal of fertility & sterility · 2026Article
- Single-Cell dissection of fibrodysplasia ossificans progressiva identifies SPP1 as a mediator of macrophage-fibroadipogenic progenitors crosstalk.Cellular and molecular life sciences : CMLS · 2026Article
- Exercise-induced myokines in metabolic regulation: mechanisms, mimetics, and translational potential.Archives of pharmacal research · 2026Review
- Macrophage and fibro-adipogenic progenitor communication in skeletal muscle regeneration: tissue homeostasis and pathogenic remodeling.Journal of leukocyte biology · 2026Review
- Stimulation of EGFR signaling in fibro-adipogenic precursors decreases adipogenesis in Duchenne muscular dystrophy.Skeletal muscle · 2026Article
- Aging induces sarcopenia by disrupting the crosstalk between the skeletal muscle microenvironment and myofibers.Journal of advanced research · 2026Review
- Cellular and molecular mechanisms of fatty infiltration in paraspinal muscles in spine-specific sarcopenia.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026Review
- The role of fibroblast growth factors in cell and cancer metabolism.FEBS letters · 2026Review
- Unraveling skeletal muscle senescence in anFrontiers in aging · 2026Article
- Fibroblast growth factor signaling induces a chondrocyte-like state of peripheral nerve fibroblast during aging.Nature communications · 2025Article
- Intramuscular adipose tissue: from progenitor to pathology.American journal of physiology. Cell physiology · 2025Review
- Sclerostin's role in bone-muscle crosstalk and osteoporosis pathogenesis.Osteoporosis and sarcopenia · 2025Review
- Deletion of EP3 prostaglandin receptor in murine macrophages aggravates diet-induced obesity by suppressing SPARC.The EMBO journal · 2025Article
- Physical Activity, Exerkines, and Their Role in Cancer Cachexia.International journal of molecular sciences · 2025Review
- Parathyroid Hormone as a Modulator of Skeletal Muscle: Insights into Bone-Muscle and Nerve-Muscle Interactions.International journal of molecular sciences · 2025Review
- Role of FGF2 in promoting osteogenic differentiation for craniofacial bone regeneration.Regenerative engineering and translational medicine · 2025Article
- Transcriptomic analysis of muscle and adipose tissues identifies myokines and adipokines contributing to lipid deposition in Taoyuan Black pigs.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2025Article
- LncRNA-MEG3 Regulates Muscle Mass and Metabolic Homeostasis by Facilitating SUZ12 Liquid-Liquid Phase Separation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aged skeletal muscle is markedly affected by fatty muscle infiltration, and strategies to reduce the occurrence of intramuscular adipocytes are urgently needed. Here, we show that fibroblast growth factor-2 (FGF-2) not only stimulates muscle growth but also promotes intramuscular adipogenesis. Using multiple screening assays upstream and downstream of microRNA (miR)-29a signaling, we located the secreted protein and adipogenic inhibitor SPARC to an FGF-2 signaling pathway that is conserved between skeletal muscle cells from mice and humans and that is activated in skeletal muscle of aged mice and humans. FGF-2 induces the miR-29a/SPARC axis through transcriptional activation of FRA-1, which binds and activates an evolutionary conserved AP-1 site element proximal in the miR-29a promoter. Genetic deletions in muscle cells and adeno-associated virus-mediated overexpression of FGF-2 or SPARC in mouse skeletal muscle revealed that this axis regulates differentiation of fibro/adipogenic progenitors in vitro and intramuscular adipose tissue (IMAT) formation in vivo. Skeletal muscle from human donors aged >75 y versus <55 y showed activation of FGF-2-dependent signaling and increased IMAT. Thus, our data highlights a disparate role of FGF-2 in adult skeletal muscle and reveals a pathway to combat fat accumulation in aged human skeletal muscle.
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