{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T00:44:13Z","timestamp":1794444253456,"version":"4.9.1"},"reference-count":104,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Skeletal muscle fibrosis is a pathological process characterized by excessive deposition of extracellular matrix (ECM). It commonly occurs in various diseases such as muscular dystrophy, aging, cancer cachexia, and muscle injury. This condition leads to destruction of muscle structure, loss of function, and impaired regeneration, significantly affecting patients\u2019 quality of life. This review systematically summarizes the molecular mechanisms underlying skeletal muscle fibrosis. Key signaling pathways include transforming growth factor-beta (TGF-\u03b2)\/Smad, yes-associated protein\/transcriptional coactivator with PDZ-binding motif (YAP\/TAZ), inflammation and immune regulation, oxidative stress, and microRNA-mediated regulation. The roles of fibro\/adipogenic progenitors (FAPs), macrophages, and myofibroblasts in this process are also discussed. Among these, the TGF-\u03b2\/Smad pathway acts as a central driver of fibrosis by promoting the differentiation of FAPs into myofibroblasts and stimulating ECM synthesis. YAP\/TAZ integrates mechanical and biochemical signals, further amplifying the fibrotic response. Inflammation, oxidative stress, and epigenetic regulators such as miRNAs and lncRNAs also contribute through complex networks. Regarding therapeutic strategies, this article highlights various interventions including pharmacological inhibition (e.g., TGF-\u03b2 inhibitors, angiotensin-converting enzyme inhibitors\/angiotensin II receptor blockers (ACEIs\/ARBs), antioxidants), gene- and RNA-targeting therapies (e.g., miRNA mimics or inhibitors), cell-based therapies (e.g., Mesenchymal Stem Cells (MSCs)), biological agents (e.g., anti-connective tissue growth factor (CTGF) antibodies), as well as physical and nutritional interventions (e.g., electroacupuncture, magnetic stimulation, natural compounds). These approaches demonstrate strong anti-fibrotic potential by modulating ECM metabolism, the immune microenvironment, and cellular behaviors. However, current research still faces challenges such as disease heterogeneity, optimal treatment timing, drug delivery issues, and long-term safety concerns. Therefore, future studies should focus on developing highly specific targeted therapies, integrating multi-omics technologies and imaging assessments, and advancing personalized combination strategies to ultimately achieve effective prevention and treatment of skeletal muscle fibrosis.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1714238","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T05:25:41Z","timestamp":1769750741000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Molecular mechanisms of skeletal muscle fibrosis and potential targeted therapeutic strategies"],"prefix":"10.3389","volume":"17","author":[{"given":"Jiahuan","family":"Gong","sequence":"first","affiliation":[{"name":"Jiangsu Key Laboratory of Tissue Engineering and Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University","place":["Nantong, Jiangsu, China"]},{"name":"Key Laboratory of Neuroregeneration of Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University","place":["Nantong, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingxuan","family":"Xu","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Tissue Engineering and Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University","place":["Nantong, Jiangsu, China"]},{"name":"Key Laboratory of Neuroregeneration of Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University","place":["Nantong, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jitai","family":"Zhang","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Tissue Engineering and Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University","place":["Nantong, Jiangsu, China"]},{"name":"Key Laboratory of Neuroregeneration of Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University","place":["Nantong, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuntian","family":"Shen","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Tissue Engineering and Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University","place":["Nantong, Jiangsu, China"]},{"name":"Key Laboratory of Neuroregeneration of Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University","place":["Nantong, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hualin","family":"Sun","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Tissue Engineering and Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University","place":["Nantong, Jiangsu, China"]},{"name":"Key Laboratory of Neuroregeneration of Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University","place":["Nantong, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingqian","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Changshu Hospital Affiliated to Soochow University, First People\u2019s Hospital of Changshu City","place":["Changshu, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-018-2955-2","article-title":"Skeletal muscle fibrosis: an overview","volume":"375","author":"Mahdy","year":"2019","journal-title":"Cell Tissue Res"},{"key":"B2","doi-asserted-by":"publisher","first-page":"117627","DOI":"10.1016\/j.bcp.2025.117627","article-title":"Chen B et\u00a0al: RIPK3 deficiency ameliorates diabetic sarcopenia through proteostasis regulation by suppressing inflammatory signaling and cellular stress pathways","volume":"244","author":"Yi","year":"2026","journal-title":"Biochem Pharmacol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"117589","DOI":"10.1016\/j.bcp.2025.117589","article-title":"Dual role of Macrophages in skeletal muscle Atrophy: Mechanisms and therapeutic strategies","volume":"244","author":"Shang","year":"2026","journal-title":"Biochem Pharmacol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.13544","article-title":"l-Carnitine relieves cachexia-related skeletal muscle fibrosis by inducing deltex E3 ubiquitin ligase 3L to negatively regulate the Runx2\/COL1A1 axis","volume":"15","author":"Lu","year":"2024","journal-title":"J cachexia sarcopenia Muscle"},{"key":"B5","doi-asserted-by":"publisher","first-page":"C1015","DOI":"10.1152\/ajpcell.00541.2024","article-title":"Role of TGF-\u03b2\/SMAD\/YAP\/TAZ signaling in skeletal muscle fibrosis","volume":"328","author":"Gallardo","year":"2025","journal-title":"Am J Physiol Cell Physiol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s10787-024-01454-7","article-title":"Celecoxib attenuates hindlimb unloading-induced muscle atrophy via suppressing inflammation, oxidative stress and ER stress by inhibiting STAT3","volume":"32","author":"Ji","year":"2024","journal-title":"Inflammopharmacology"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/bs.ctdb.2024.01.012","article-title":"Skeletal muscle niche, at the crossroad of cell\/cell communications","volume":"158","author":"Theret","year":"2024","journal-title":"Curr Top Dev Biol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"104220","DOI":"10.1016\/j.etap.2023.104220","article-title":"Simvastatin attenuates aluminium chloride-induced neurobehavioral impairments through activation of TGF-\u03b21\/SMAD2 and GSK3\u03b2\/\u03b2-catenin signalling pathways","volume":"102","author":"Atef","year":"2023","journal-title":"Environ Toxicol Pharmacol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.add9984","article-title":"Single-cell and spatial transcriptomics identify a macrophage population associated with skeletal muscle fibrosis","volume":"9","author":"Coulis","year":"2023","journal-title":"Sci Adv"},{"key":"B10","doi-asserted-by":"publisher","first-page":"29393","DOI":"10.1038\/s41598-024-76415-9","article-title":"miR-1, miR-133a, miR-29b and skeletal muscle fibrosis in chronic limb-threatening ischaemia","volume":"14","author":"Keane","year":"2024","journal-title":"Sci Rep"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0186719","article-title":"Reduction in skeletal muscle fibrosis of spontaneously hypertensive rats after laceration by microRNA targeting angiotensin II receptor","volume":"12","author":"Stilhano","year":"2017","journal-title":"PloS One"},{"key":"B12","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1007\/978-3-319-72041-8_6","article-title":"Nanoparticles-caused oxidative imbalance","volume":"1048","author":"Zuberek","year":"2018","journal-title":"Adv Exp Med Biol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.14336\/AD.2025.1162","article-title":"Rethinking muscle aging through the lens of fibro-adipogenic progenitors","author":"Zhang","year":"2025","journal-title":"Aging Dis"},{"key":"B14","doi-asserted-by":"publisher","first-page":"148873","DOI":"10.1016\/j.gene.2024.148873","article-title":"Sarcopenia is attenuated by mairin in SAMP8 mice via the inhibition of FAPs fibrosis through the AMPK-TGF-\u03b2-SMAD axis","volume":"931","author":"Zhong","year":"2024","journal-title":"Gene"},{"key":"B15","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1007\/s00018-023-05096-w","article-title":"MuSCs and IPCs: roles in skeletal muscle homeostasis, aging and injury","volume":"81","author":"Jiang","year":"2024","journal-title":"Cell Mol Life Sci"},{"key":"B16","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1111\/dmcn.16006","article-title":"Muscle satellite cells and fibro-adipogenic progenitors from muscle contractures of children with cerebral palsy have impaired regenerative capacity","volume":"67","author":"Loomis","year":"2025","journal-title":"Dev Med Child Neurol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"C895","DOI":"10.1152\/ajpcell.00245.2023","article-title":"Thrown for a loop: fibro-adipogenic progenitors in skeletal muscle fibrosis","volume":"325","author":"Loomis","year":"2023","journal-title":"Am J Physiol Cell Physiol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1186\/s13018-024-04733-9","article-title":"miR-27b-3p reduces muscle fibrosis during chronic skeletal muscle injury by targeting TGF-\u03b2R1\/Smad pathway","volume":"19","author":"Yao","year":"2024","journal-title":"J Orthop Surg Res"},{"key":"B19","doi-asserted-by":"publisher","first-page":"2201","DOI":"10.1016\/j.cmet.2021.10.001","article-title":"Human skeletal muscle CD90(+) fibro-adipogenic progenitors are associated with muscle degeneration in type 2 diabetic patients","volume":"33","author":"Farup","year":"2021","journal-title":"Cell Metab"},{"key":"B20","doi-asserted-by":"publisher","first-page":"101277","DOI":"10.1016\/j.mam.2024.101277","article-title":"Fibro-adipogenic progenitors in physiological adipogenesis and intermuscular adipose tissue remodeling","volume":"97","author":"Flores-Opazo","year":"2024","journal-title":"Mol aspects Med"},{"key":"B21","doi-asserted-by":"publisher","first-page":"8273","DOI":"10.1038\/s41467-023-43579-3","article-title":"DPPIV(+) fibro-adipogenic progenitors form the niche of adult skeletal muscle self-renewing resident macrophages","volume":"14","author":"Babaeijandaghi","year":"2023","journal-title":"Nat Commun"},{"key":"B22","doi-asserted-by":"publisher","first-page":"5233","DOI":"10.1038\/s41467-025-60627-2","article-title":"Complementing muscle regeneration-fibro-adipogenic progenitor and macrophage-mediated repair of elderly human skeletal muscle","volume":"16","author":"Brorson","year":"2025","journal-title":"Nat Commun"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3390\/cells12091214","article-title":"Macrophage involvement in aging-associated skeletal muscle regeneration","volume":"12","author":"Cui","year":"2023","journal-title":"Cells"},{"key":"B24","doi-asserted-by":"publisher","first-page":"108997","DOI":"10.1016\/j.celrep.2021.108997","article-title":"A stromal progenitor and ILC2 niche promotes muscle eosinophilia and fibrosis-associated gene expression","volume":"35","author":"Kastenschmidt","year":"2021","journal-title":"Cell Rep"},{"key":"B25","doi-asserted-by":"publisher","first-page":"32633","DOI":"10.1038\/s41598-025-12734-9","article-title":"Tofogliflozin ameliorates cardiotoxin induced skeletal muscle injury and fibrosis in obesity","volume":"15","author":"Bilal","year":"2025","journal-title":"Sci Rep"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M708590200","article-title":"Meichroacidin containing the membrane occupation and recognition nexus motif is essential for spermatozoa morphogenesis","volume":"283","author":"Tokuhiro","year":"2008","journal-title":"J Biol Chem"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M704146200","article-title":"Relationships between transforming growth factor-beta1, myostatin, and decorin: implications for skeletal muscle fibrosis","volume":"282","author":"Zhu","year":"2007","journal-title":"J Biol Chem"},{"key":"B28","doi-asserted-by":"publisher","first-page":"117039","DOI":"10.1016\/j.jep.2023.117039","article-title":"Rehmannia glutinosa Libosch and Cornus officinalis Sieb herb couple ameliorates renal interstitial fibrosis in CKD rats by inhibiting the TGF-\u03b21\/MAPK signaling pathway","volume":"318","author":"Zhu","year":"2024","journal-title":"J ethnopharmacology"},{"key":"B29","doi-asserted-by":"publisher","first-page":"124261","DOI":"10.1016\/j.ijpharm.2024.124261","article-title":"Platelet membrane biomimetic nanoparticle-targeted delivery of TGF-\u03b21 siRNA attenuates renal inflammation and fibrosis","volume":"659","author":"Fei","year":"2024","journal-title":"Int J pharmaceutics"},{"key":"B30","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1186\/s12891-021-04569-y","article-title":"P2Y2 promotes fibroblasts activation and skeletal muscle fibrosis through AKT, ERK, and PKC","volume":"22","author":"Chen","year":"2021","journal-title":"BMC Musculoskelet Disord"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.70144","article-title":"Decorin deficiency promotes D-galactose-induced skeletal muscle atrophy and fibrosis by regulating ITGB1\/akt\/mTOR signalling pathway","volume":"16","author":"Luo","year":"2025","journal-title":"J cachexia sarcopenia Muscle"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-013-1642-6","article-title":"Inhibition of the angiotensin-converting enzyme decreases skeletal muscle fibrosis in dystrophic mice by a diminution in the expression and activity of connective tissue growth factor (CTGF\/CCN-2)","volume":"353","author":"Morales","year":"2013","journal-title":"Cell Tissue Res"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1113\/EP089375","article-title":"Angiotensin-converting enzyme inhibitor prevents skeletal muscle fibrosis in diabetic mice","volume":"106","author":"Kakutani","year":"2021","journal-title":"Exp Physiol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.7549","article-title":"Mangiferin prevents hepatocyte epithelial-mesenchymal transition in liver fibrosis via targeting HSP27-mediated JAK2\/STAT3 and TGF-\u03b21\/Smad pathway","volume":"36","author":"Zhang","year":"2022","journal-title":"Phytotherapy research: PTR"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.917428","article-title":"Yi-shen-hua-shi granule alleviates adriamycin-induced glomerular fibrosis by suppressing the BMP2\/smad signaling pathway","volume":"13","author":"Tan","year":"2022","journal-title":"Front Pharmacol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1007\/s10522-024-10093-y","article-title":"The SGLT2 inhibitor empagliflozin inhibits skeletal muscle fibrosis in naturally aging male mice through the AMPK\u03b1\/MMP9\/TGF-\u03b21\/Smad pathway","volume":"25","author":"Huang","year":"2024","journal-title":"Biogerontology"},{"key":"B37","doi-asserted-by":"publisher","first-page":"e33062","DOI":"10.1016\/j.heliyon.2024.e33062","article-title":"MiR-21 regulates skeletal muscle atrophy and fibrosis by targeting TGF-beta\/SMAD7-SMAD2\/3 signaling pathway","volume":"10","author":"Song","year":"2024","journal-title":"Heliyon"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1093\/abbs\/gmx052","article-title":"miR-146a-5p acts as a negative regulator of TGF-\u03b2 signaling in skeletal muscle after acute contusion","volume":"49","author":"Sun","year":"2017","journal-title":"Acta Biochim Biophys Sin (Shanghai)"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00721.2015","article-title":"Sulforaphane mitigates muscle fibrosis in mdx mice via Nrf2-mediated inhibition of TGF-\u03b2\/Smad signaling","volume":"120","author":"Sun","year":"2016","journal-title":"J Appl Physiol (1985)"},{"key":"B40","doi-asserted-by":"publisher","first-page":"pky043","DOI":"10.1093\/jncics\/pky043","article-title":"Skeletal muscle fibrosis in pancreatic cancer patients with respect to survival","volume":"2","author":"Judge","year":"2018","journal-title":"JNCI Cancer Spectr"},{"key":"B41","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.matbio.2019.01.002","article-title":"Denervation-induced skeletal muscle fibrosis is mediated by CTGF\/CCN2 independently of TGF-\u03b2","volume":"82","author":"Rebolledo","year":"2019","journal-title":"Matrix biology: J Int Soc Matrix Biol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.859723","article-title":"Paeoniflorin ameliorates skeletal muscle atrophy in chronic kidney disease via AMPK\/SIRT1\/PGC-1\u03b1-mediated oxidative stress and mitochondrial dysfunction","volume":"13","author":"Li","year":"2022","journal-title":"Front Pharmacol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2023.1017660","article-title":"Single-cell transcriptome dynamics of the autotaxin-lysophosphatidic acid axis during muscle regeneration reveal proliferative effects in mesenchymal fibro-adipogenic progenitors","volume":"11","author":"Contreras","year":"2023","journal-title":"Front Cell Dev Biol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2024.08.005","article-title":"Involvement of lysophosphatidic acid-LPA(1)-YAP signaling in healthy and pathological FAPs migration","volume":"133","author":"Bock-Pereda","year":"2024","journal-title":"Matrix biology: J Int Soc Matrix Biol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.matbio.2024.05.001","article-title":"LPA-induced expression of CCN2 in muscular fibro\/adipogenic progenitors (FAPs): Unraveling cellular communication networks","volume":"130","author":"C\u00f3rdova-Casanova","year":"2024","journal-title":"Matrix Biol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12578","article-title":"Aging of the skeletal muscle extracellular matrix drives a stem cell fibrogenic conversion","volume":"16","author":"Stearns-Reider","year":"2017","journal-title":"Aging Cell"},{"key":"B47","doi-asserted-by":"publisher","first-page":"1457","DOI":"10.3892\/etm.2021.10892","article-title":"Electroacupuncture regulates inflammation, collagen deposition and macrophage function in skeletal muscle through the TGF-\u03b21\/Smad3\/p38\/ERK1\/2 pathway","volume":"22","author":"Han","year":"2021","journal-title":"Exp Ther Med"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2209976119","article-title":"TNF\u03b1 and IFN\u03b3 cooperate for efficient pro- to anti-inflammatory transition of macrophages during muscle regeneration","volume":"119","author":"Babaeijandaghi","year":"2022","journal-title":"Proc Natl Acad Sci U.S.A"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.02.053","article-title":"Type 2 innate signals stimulate fibro\/adipogenic progenitors to facilitate muscle regeneration","volume":"153","author":"Heredia","year":"2013","journal-title":"Cell"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.3390\/biom15010020","article-title":"The change of skeletal muscle caused by inflammation in obesity as the key path to fibrosis: thoughts on mechanisms and intervention strategies","volume":"15","author":"Li","year":"2024","journal-title":"Biomolecules"},{"key":"B51","doi-asserted-by":"publisher","first-page":"115664","DOI":"10.1016\/j.bcp.2023.115664","article-title":"Oxidative stress: Roles in skeletal muscle atrophy","volume":"214","author":"Zhang","year":"2023","journal-title":"Biochem Pharmacol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.533690","article-title":"Hydrogen sulfide alleviates skeletal muscle fibrosis via attenuating inflammation and oxidative stress","volume":"11","author":"Zhao","year":"2020","journal-title":"Front Physiol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2022.115407","article-title":"Chronic kidney disease-induced muscle atrophy: Molecular mechanisms and promising therapies","volume":"208","author":"Wang","year":"2023","journal-title":"Biochem Pharmacol"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00240.2015","article-title":"Heightened TWEAK-NF-\u03baB signaling and inflammation-associated fibrosis in paralyzed muscles of men with chronic spinal cord injury","volume":"310","author":"Yarar-Fisher","year":"2016","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.4081\/ejtm.2023.12037","article-title":"Angiotensin-(1-7) improves skeletal muscle regeneration","volume":"33","author":"Valero-Breton","year":"2023","journal-title":"Eur J Transl Myol"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.2c05246","article-title":"Highland barley tea polyphenols extract alleviates skeletal muscle fibrosis in mice by reducing oxidative stress, inflammation, and cell senescence","volume":"71","author":"Nie","year":"2023","journal-title":"J Agric Food Chem"},{"key":"B57","doi-asserted-by":"publisher","first-page":"6669","DOI":"10.1016\/j.cell.2024.08.041","article-title":"Profound cellular defects attribute to muscular pathogenesis in the rhesus monkey model of Duchenne muscular dystrophy","volume":"187","author":"Ren","year":"2024","journal-title":"Cell"},{"key":"B58","doi-asserted-by":"publisher","first-page":"16093","DOI":"10.1038\/s41598-024-66918-w","article-title":"Dynamics of single-nuclei transcriptomic profiling of adipose tissue from diverse anatomical locations during mouse aging process","volume":"14","author":"Wu","year":"2024","journal-title":"Sci Rep"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13659","article-title":"Lysyl oxidase-like 2 inhibitor rescues D-galactose-induced skeletal muscle fibrosis","volume":"21","author":"Wu","year":"2022","journal-title":"Aging Cell"},{"key":"B60","doi-asserted-by":"publisher","first-page":"115664","DOI":"10.1016\/j.bcp.2023.115664","article-title":"Qi L et\u00a0al: Oxidative stress: Roles in skeletal muscle atrophy","volume":"214","author":"Zhang","year":"2023","journal-title":"Biochem Pharmacol"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12560","article-title":"Sarcopenia is attenuated by TRB3 knockout in aging mice via the alleviation of atrophy and fibrosis of skeletal muscles","volume":"11","author":"Shang","year":"2020","journal-title":"J Cachexia Sarcopenia Muscle"},{"key":"B62","doi-asserted-by":"publisher","first-page":"175476","DOI":"10.1016\/j.ejphar.2022.175476","article-title":"Irisin ameliorates D-galactose-induced skeletal muscle fibrosis via the PI3K\/Akt pathway","volume":"939","author":"Wu","year":"2023","journal-title":"Eur J Pharmacol"},{"key":"B63","doi-asserted-by":"publisher","first-page":"117326","DOI":"10.1016\/j.bcp.2025.117326","article-title":"Myokine-mediated muscle-organ interactions: Molecular mechanisms and clinical significance","volume":"242","author":"Yi","year":"2025","journal-title":"Biochem Pharmacol"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.947387","article-title":"Adenosine monophosphate activated protein kinase contributes to skeletal muscle health through the control of mitochondrial function","volume":"13","author":"Yan","year":"2022","journal-title":"Front Pharmacol"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.13526","article-title":"Aerobic exercise suppresses CCN2 secretion from senescent muscle stem cells and boosts muscle regeneration in aged mice","volume":"15","author":"Li","year":"2024","journal-title":"J Cachexia Sarcopenia Muscle"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1111\/cns.70657","article-title":"AMPK\/SIRT1\/PGC-1\u03b1 Signaling pathway: molecular mechanisms and targeted strategies from energy homeostasis regulation to disease therapy","volume":"31","author":"Chen","year":"2025","journal-title":"CNS Neurosci Ther"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2016.3856","article-title":"MicroRNA-351 inhibits denervation-induced muscle atrophy by targeting TRAF6","volume":"12","author":"He","year":"2016","journal-title":"Exp Ther Med"},{"key":"B68","doi-asserted-by":"publisher","first-page":"456","DOI":"10.21037\/atm.2019.08.39","article-title":"miR-125b-5p targeting TRAF6 relieves skeletal muscle atrophy induced by fasting or denervation","volume":"7","author":"Qiu","year":"2019","journal-title":"Ann Transl Med"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2018.04.005","article-title":"miR-24 and miR-122 negatively regulate the transforming growth factor-\u03b2\/smad signaling pathway in skeletal muscle fibrosis","volume":"11","author":"Sun","year":"2018","journal-title":"Mol Ther Nucleic Acids"},{"key":"B70","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.matbio.2018.07.003","article-title":"Exosomes and exosomal miRNAs from muscle-derived fibroblasts promote skeletal muscle fibrosis","volume":"74","author":"Zanotti","year":"2018","journal-title":"Matrix Biol"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26020752","article-title":"Type 2 Diabetes Induces Mitochondrial Dysfunction in Zebrafish Skeletal Muscle Leading to Diabetic Myopathy via the miR-139-5p\/NAMPT Pathway","volume":"26","author":"Chen","year":"2025","journal-title":"Int J Mol Sci"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.16508","article-title":"Long non-coding RNA MFAT1 promotes skeletal muscle fibrosis by modulating the miR-135a-5p-Tgfbr2\/Smad4 axis as a ceRNA","volume":"25","author":"Lin","year":"2021","journal-title":"J Cell Mol Med"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-025-01620-9","article-title":"circSP199a, a circularized RNA sponge targeting miR-199a-5p and -3p, mitigates mouse cardiac hypertrophy and fibrosis","volume":"47","author":"Wu","year":"2026","journal-title":"Acta pharmacologica Sin"},{"key":"B75","doi-asserted-by":"publisher","first-page":"178107","DOI":"10.1016\/j.ejphar.2025.178107","article-title":"MicroRNA-29a attenuates inflammation and fibrosis in an animal model of NASH through MCJ inhibition and hippo pathway regulation","volume":"1005","author":"Yang","year":"2025","journal-title":"Eur J Pharmacol"},{"key":"B76","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1038\/s41419-025-07956-8","article-title":"Long noncoding RNA H19 promotes the acquisition of a mesenchymal-like invasive phenotype in mesothelial primary cells through an HDAC1-mediated WT1\/Sp1 switch","volume":"16","author":"Bontempi","year":"2025","journal-title":"Cell Death Dis"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20102446","article-title":"Role of transforming growth factor-\u03b2 in skeletal muscle fibrosis: A review","volume":"20","author":"Ismaeel","year":"2019","journal-title":"Int J Mol Sci"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1900814","article-title":"Tuning macrophage phenotype to mitigate skeletal muscle fibrosis","volume":"204","author":"Stepien","year":"2020","journal-title":"J Immunol"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22168861","article-title":"Antagonizing S1P(3) receptor with cell-penetrating pepducins in skeletal muscle fibrosis","volume":"22","author":"Corvino","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1002\/cbf.3797","article-title":"Development of skeletal muscle fibrosis in a rodent model of cancer cachexia","volume":"41","author":"Washington","year":"2023","journal-title":"Cell Biochem Funct"},{"key":"B81","doi-asserted-by":"publisher","first-page":"F1658","DOI":"10.1152\/ajprenal.00314.2018","article-title":"Skeletal muscle fibrosis is associated with decreased muscle inflammation and weakness in patients with chronic kidney disease","volume":"315","author":"Abramowitz","year":"2018","journal-title":"Am J Physiol Renal Physiol"},{"key":"B82","doi-asserted-by":"publisher","first-page":"48","DOI":"10.2106\/JBJS.O.00545","article-title":"Angiotensin-(1-7) attenuates skeletal muscle fibrosis and stiffening in a mouse model of extremity sarcoma radiation therapy","volume":"98","author":"Willey","year":"2016","journal-title":"J Bone Joint Surg Am volume"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0093449","article-title":"ACE2 is augmented in dystrophic skeletal muscle and plays a role in decreasing associated fibrosis","volume":"9","author":"Riquelme","year":"2014","journal-title":"PloS One"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.234948","article-title":"TNAP limits TGF-\u03b2-dependent cardiac and skeletal muscle fibrosis by inactivating the SMAD2\/3 transcription factors","volume":"132","author":"Arn\u00f2","year":"2019","journal-title":"J Cell Sci"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S450599","article-title":"Macrophage-myofibroblast transition as a potential origin for skeletal muscle fibrosis after injury via complement system activation","volume":"17","author":"Qi","year":"2024","journal-title":"J Inflammation Res"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1007\/s12576-016-0492-x","article-title":"Astaxanthin supplementation attenuates immobilization-induced skeletal muscle fibrosis via suppression of oxidative stress","volume":"67","author":"Maezawa","year":"2017","journal-title":"J Physiol Sci"},{"key":"B87","doi-asserted-by":"publisher","first-page":"8259","DOI":"10.1080\/10408398.2025.2498676","article-title":"Nutritional strategies targeting age-related skeletal muscle fibrosis: underlying mechanisms","volume":"65","author":"Cuijpers","year":"2025","journal-title":"Crit Rev Food Sci Nutr"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1097\/BPB.0000000000000117","article-title":"Osteoactivin attenuates skeletal muscle fibrosis after distraction osteogenesis by promoting extracellular matrix degradation\/remodeling","volume":"24","author":"Tonogai","year":"2015","journal-title":"J Pediatr Orthop B"},{"key":"B89","doi-asserted-by":"publisher","first-page":"5543468","DOI":"10.1155\/2021\/5543468","article-title":"The combination of electroacupuncture and massage therapy alleviates myofibroblast transdifferentiation and extracellular matrix production in blunt trauma-induced skeletal muscle fibrosis","volume":"2021","author":"Zhao","year":"2021","journal-title":"Evid Based Complement Alternat Med"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1093\/stmcls\/sxae058","article-title":"Mesenchymal stromal cell transplantation ameliorates fibrosis and microRNA dysregulation in skeletal muscle ischemia","volume":"42","author":"Sanz-Nogu\u00e9s","year":"2024","journal-title":"Stem Cells (Dayton Ohio)"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202000240RR","article-title":"Blocking CTGF\/CCN2 reduces established skeletal muscle fibrosis in a rat model of overuse injury","volume":"34","author":"Barbe","year":"2020","journal-title":"FASEB J"},{"key":"B92","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1186\/s40634-018-0143-7","article-title":"Platelet-rich plasma does not reduce skeletal muscle fibrosis after distraction osteogenesis","volume":"5","author":"Tonogai","year":"2018","journal-title":"J Exp Orthop"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.2147\/BTT.S508221","article-title":"Targeted therapy for skeletal muscle fibrosis: regulation of myostatin, TGF-\u03b2, MMP, and TIMP to maintain extracellular matrix homeostasis","volume":"19","author":"Dewi","year":"2025","journal-title":"Biologics"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12010044","article-title":"Potential therapeutic strategies for skeletal muscle atrophy","volume":"12","author":"Huang","year":"2022","journal-title":"Antioxidants (Basel Switzerland)"},{"key":"B95","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1186\/s13018-025-06400-z","article-title":"Mechanistic effects of percutaneous needle fasciotomy combined with stretching on early-stage skeletal muscle fibrosis in rats: focus on the TGF-\u03b21\/Smad signaling pathway","volume":"20","author":"Zhang","year":"2025","journal-title":"J orthopaedic Surg Res"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1097\/PHM.0000000000001042","article-title":"Effects of twitch contraction induced by magnetic stimulation on expression of skeletal muscle fibrosis related genes and limited range of motion in rats","volume":"98","author":"Kubo","year":"2019","journal-title":"Am J Phys Med Rehabil"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.8b00739","article-title":"Effects of geniposide from gardenia fruit pomace on skeletal-muscle fibrosis","volume":"66","author":"Pan","year":"2018","journal-title":"J Agric Food Chem"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.202300347","article-title":"Nutritional strategies for muscle atrophy: current evidence and underlying mechanisms","volume":"68","author":"Shen","year":"2024","journal-title":"Mol Nutr Food Res"},{"key":"B99","doi-asserted-by":"publisher","first-page":"e70099","DOI":"10.1002\/cbin.70099","article-title":"Sodium tanshinone IIA sulfonate ameliorates fibrosis of skeletal muscle injury by regulating transforming growth factor-\u03b21\/smad3 and phosphoinositide 3-kinase\/protein kinase B\/cyclooxygenase-2 signaling pathways","volume":"50","author":"Ding","year":"2026","journal-title":"Cell Biol Int"},{"key":"B100","doi-asserted-by":"publisher","first-page":"3946320241309004","DOI":"10.1177\/03946320241309004","article-title":"Hesperidin ameliorates thioacetamide-induced liver fibrosis via antioxidative and anti-inflammatory mechanisms targeting TGF-\u03b2\/\u03b1-SMA pathways in rats","volume":"38","author":"Megahed","year":"2024","journal-title":"Int J immunopathology Pharmacol"},{"key":"B101","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1038\/s41598-020-78747-8","article-title":"Non-invasive assessment of skeletal muscle fibrosis in mice using nuclear magnetic resonance imaging and ultrasound shear wave elastography","volume":"11","author":"Martins-Bach","year":"2021","journal-title":"Sci Rep"},{"key":"B102","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.exger.2019.04.008","article-title":"Inhibition of TLR9 attenuates skeletal muscle fibrosis in aged sarcopenic mice via the p53\/SIRT1 pathway","volume":"122","author":"Lyu","year":"2019","journal-title":"Exp Gerontol"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2024.12.005","article-title":"Advances in biomaterial-based tissue engineering for peripheral nerve injury repair","volume":"46","author":"Yao","year":"2025","journal-title":"Bioactive materials"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2021.10.009","article-title":"Diabetes-induced skeletal muscle fibrosis: Fibro-adipogenic precursors at work","volume":"33","author":"Chazaud","year":"2021","journal-title":"Cell Metab"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1714238\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T09:26:55Z","timestamp":1771925215000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1714238\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,30]]},"references-count":104,"alternative-id":["10.3389\/fimmu.2026.1714238"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1714238","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,30]]},"article-number":"1714238"}}