{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:16:11Z","timestamp":1790813771795,"version":"4.1.0"},"reference-count":70,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,4,23]],"date-time":"2020-04-23T00:00:00Z","timestamp":1587600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["Biotechnology and Biological Sciences Research Council"],"award-info":[{"award-number":["Biotechnology and Biological Sciences Research Council"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Irish Research Council Laureate","award":["IRCLA\/2017\/101"],"award-info":[{"award-number":["IRCLA\/2017\/101"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Ageing is associated with disrupted redox signalling and increased circulating inflammatory cytokines. Skeletal muscle homeostasis depends on the balance between muscle hypertrophy, atrophy and regeneration, however during ageing this balance is disrupted. The molecular pathways underlying the age-related decline in muscle regenerative potential remain elusive. microRNAs are conserved robust gene expression regulators in all tissues including skeletal muscle. Here, we studied satellite cells from adult and old mice to demonstrate that inhibition of miR-21 in satellite cells from old mice improves myogenesis. We determined that increased levels of proinflammatory cytokines, TNF\u03b1 and IL6, as well as H2O2, increased miR-21 expression in primary myoblasts, which in turn resulted in their decreased viability and myogenic potential. Inhibition of miR-21 function rescued the decreased size of myotubes following TNF\u03b1 or IL6 treatment. Moreover, we demonstrated that miR-21 could inhibit myogenesis in vitro via regulating IL6R, PTEN and FOXO3 signalling. In summary, upregulation of miR-21 in satellite cells and muscle during ageing may occur in response to elevated levels of TNF\u03b1 and IL6, within satellite cells or myofibrillar environment contributing to skeletal muscle ageing and potentially a disease-related decline in potential for muscle regeneration.<\/jats:p>","DOI":"10.3390\/antiox9040345","type":"journal-article","created":{"date-parts":[[2020,4,23]],"date-time":"2020-04-23T10:46:22Z","timestamp":1587638782000},"page":"345","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Inflamma-miR-21 Negatively Regulates Myogenesis during Ageing"],"prefix":"10.3390","volume":"9","author":[{"given":"Maria","family":"Borja-Gonzalez","sequence":"first","affiliation":[{"name":"School of Medicine, Physiology, National University of Ireland, H91 W5P7 Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose C.","family":"Casas-Martinez","sequence":"additional","affiliation":[{"name":"School of Medicine, Physiology, National University of Ireland, H91 W5P7 Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"McDonagh","sequence":"additional","affiliation":[{"name":"School of Medicine, Physiology, National University of Ireland, H91 W5P7 Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8166-8800","authenticated-orcid":false,"given":"Katarzyna","family":"Goljanek-Whysall","sequence":"additional","affiliation":[{"name":"School of Medicine, Physiology, National University of Ireland, H91 W5P7 Galway, Ireland"},{"name":"Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool L7 8TJ, UK"},{"name":"The Medical Research Council Versus Arthritis Centre for Integrated Research into Musculoskeletal Ageing (CIMA), Liverpool L7 8TJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1152\/physrev.00061.2017","article-title":"Sarcopenia: Aging-Related Loss of Muscle Mass and Function","volume":"99","author":"Larsson","year":"2019","journal-title":"Physiol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.coph.2015.04.003","article-title":"Cachexia and sarcopenia: Mechanisms and potential targets for intervention","volume":"22","author":"Busquets","year":"2015","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"R1485","DOI":"10.1152\/ajpregu.00467.2009","article-title":"Aging and its effects on inflammation in skeletal muscle at rest and following exercise-induced muscle injury","volume":"298","author":"Peake","year":"2010","journal-title":"Am. J. Physiol. Integr. Comp. Physiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.cyto.2017.11.006","article-title":"Tumor-derived cytokines impair myogenesis and alter the skeletal muscle immune microenvironment","volume":"107","author":"Hogan","year":"2018","journal-title":"Cytokine"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1089\/ars.2016.6782","article-title":"Redox Control of Skeletal Muscle Regeneration","volume":"27","author":"Pialoux","year":"2017","journal-title":"Antioxidants Redox Signal."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.ebiom.2019.10.034","article-title":"Skeletal muscle as potential central link between sarcopenia and immune senescence","volume":"49","author":"Nelke","year":"2019","journal-title":"EBioMedicine"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.1111\/febs.14417","article-title":"Chronic inflammation in skeletal muscle impairs satellite cells function during regeneration: Can physical exercise restore the satellite cell niche?","volume":"285","author":"Perandini","year":"2018","journal-title":"FEBS J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1016\/S1357-2725(03)00042-6","article-title":"Muscle satellite cells","volume":"35","author":"Morgan","year":"2003","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1126\/science.1144090","article-title":"Increased Wnt Signaling During Aging Alters Muscle Stem Cell Fate and Increases Fibrosis","volume":"317","author":"Brack","year":"2007","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1634\/stemcells.2006-0372","article-title":"A Population of Myogenic Stem Cells That Survives Skeletal Muscle Aging","volume":"25","author":"Collins","year":"2007","journal-title":"STEM CELLS"},{"key":"ref_11","first-page":"E151","article-title":"Satellite cell content is specifically reduced in type II skeletal muscle fibers in the elderly","volume":"292","author":"Verdijk","year":"2007","journal-title":"Am. J. Physiol. Metab."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1111\/acel.12442","article-title":"Age-related changes in miR-143-3p:Igfbp5 interactions affect muscle regeneration","volume":"15","author":"McCormick","year":"2016","journal-title":"Aging Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/j.trecan.2019.07.010","article-title":"Impaired Muscle Regeneration in Cancer-Associated Cachexia","volume":"5","author":"Arneson","year":"2019","journal-title":"Trends Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1038\/nm.3918","article-title":"The central role of muscle stem cells in regenerative failure with aging","volume":"21","author":"Blau","year":"2015","journal-title":"Nat. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1152\/japplphysiol.00961.2018","article-title":"Micro(RNA)-managing muscle wasting","volume":"127","author":"Sannicandro","year":"2019","journal-title":"J. Appl. Physiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1097\/MCO.0000000000000645","article-title":"MicroRNAs as potential therapeutic targets for muscle wasting during cancer cachexia","volume":"23","author":"Sannicandro","year":"2020","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1007\/s00335-016-9643-x","article-title":"Ageing in relation to skeletal muscle dysfunction: Redox homoeostasis to regulation of gene expression","volume":"27","author":"Iwanejko","year":"2016","journal-title":"Mamm. Genome"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1152\/japplphysiol.00932.2006","article-title":"MicroRNA-1 and microRNA-133a expression are decreased during skeletal muscle hypertrophy","volume":"102","author":"McCarthy","year":"2007","journal-title":"J. Appl. Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3378","DOI":"10.1242\/dev.108787","article-title":"myomiR-dependent switching of BAF60 variant incorporation into Brg1 chromatin remodeling complexes during embryo myogenesis","volume":"141","author":"Mok","year":"2014","journal-title":"Development"},{"key":"ref_20","first-page":"3590","article-title":"Regulation of multiple target genes by miR-1 and miR-206 is pivotal for C2C12 myoblast differentiation","volume":"139","author":"Pais","year":"2012","journal-title":"Development"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"11936","DOI":"10.1073\/pnas.1105362108","article-title":"MicroRNA regulation of the paired-box transcription factor Pax3 confers robustness to developmental timing of myogenesis","volume":"108","author":"Sweetman","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3258","DOI":"10.1172\/JCI46267","article-title":"Mice lacking microRNA 133a develop dynamin 2\u2013dependent centronuclear myopathy","volume":"121","author":"Liu","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.arr.2015.08.007","article-title":"microRNAs: Modulators of the underlying pathophysiology of sarcopenia?","volume":"24","author":"Brown","year":"2015","journal-title":"Ageing Res. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Goljanek-Whysall, K., Soriano-Arroquia, A., McCormick, R., Chinda, C.A., and McDonagh, B. (2020). miR-181a Regulates p62\/SQSTM1, Parkin and Protein DJ-1 Promoting Mitochondrial Dynamics in Skeletal Muscle Ageing. Aging Cell.","DOI":"10.1101\/805176"},{"key":"ref_25","first-page":"E1333","article-title":"Aging differentially affects human skeletal muscle microRNA expression at rest and after an anabolic stimulus of resistance exercise and essential amino acids","volume":"295","author":"Drummond","year":"2008","journal-title":"Am. J. Physiol. Metab."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"524","DOI":"10.18632\/aging.100677","article-title":"Genome-wide profiling of the microRNA-mRNA regulatory network in skeletal muscle with aging","volume":"6","author":"Kim","year":"2014","journal-title":"Aging"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1007\/s10522-016-9638-8","article-title":"The functional consequences of age-related changes in microRNA expression in skeletal muscle","volume":"17","author":"House","year":"2016","journal-title":"Biogerontology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4525","DOI":"10.1073\/pnas.1402714111","article-title":"Microvesicles containing miRNAs promote muscle cell death in cancer cachexia via TLR7","volume":"111","author":"He","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"17016","DOI":"10.1073\/pnas.0708115104","article-title":"Distinctive patterns of microRNA expression in primary muscular disorders","volume":"104","author":"Eisenberg","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1038\/nature10834","article-title":"Maintenance of muscle stem-cell quiescence by microRNA-489","volume":"482","author":"Cheung","year":"2012","journal-title":"Nature"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/j.mad.2012.09.004","article-title":"Age-related differences in the expression of circulating microRNAs: miR-21 as a new circulating marker of inflammaging","volume":"133","author":"Olivieri","year":"2012","journal-title":"Mech. Ageing Dev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2018\/7671850","article-title":"Analysis of Plasma MicroRNAs as Predictors and Biomarkers of Aging and Frailty in Humans","volume":"2018","author":"Rusanova","year":"2018","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2148","DOI":"10.1016\/j.celrep.2018.10.074","article-title":"Activation of miR-21-Regulated Pathways in Immune Aging Selects against Signatures Characteristic of Memory T Cells","volume":"25","author":"Kim","year":"2018","journal-title":"Cell Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"19","DOI":"10.3389\/fimmu.2015.00019","article-title":"Turning 21: Induction of miR-21 as a Key Switch in the Inflammatory Response","volume":"6","author":"Sheedy","year":"2015","journal-title":"Front. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1038\/nature09284","article-title":"OncomiR addiction in an in vivo model of microRNA-21-induced pre-B-cell lymphoma","volume":"467","author":"Medina","year":"2010","journal-title":"Nature"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"21909","DOI":"10.1074\/jbc.M114.561845","article-title":"Involvement of MicroRNAs in the Regulation of Muscle Wasting during Catabolic Conditions*","volume":"289","author":"Soares","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1083\/jcb.201105013","article-title":"PAI-1\u2013regulated miR-21 defines a novel age-associated fibrogenic pathway in muscular dystrophy","volume":"196","author":"Ardite","year":"2012","journal-title":"J. Cell Biol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Bai, L., Liang, R., Yang, Y., Hou, X., Wang, Z., Zhu, S., Wang, C., Tang, Z., and Li, K. (2015). MicroRNA-21 Regulates PI3K\/Akt\/mTOR Signaling by Targeting TGF\u03b2I during Skeletal Muscle Development in Pigs. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0119396"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Soriano-Arroquia, A., Clegg, P.D., Molloy, A.P., and Goljanek-Whysall, K. (2017). Preparation and Culture of Myogenic Precursor Cells\/Primary Myoblasts from Skeletal Muscle of Adult and Aged Humans. J. Vis. Exp., e55047.","DOI":"10.3791\/55047-v"},{"key":"ref_40","first-page":"93","article-title":"Alterations in the in vitro and in vivo regulation of muscle regeneration in healthy ageing and the influence of sarcopenia","volume":"9","author":"Meyer","year":"2017","journal-title":"J. Cachex-Sarcopenia Muscle"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/1476-9255-8-41","article-title":"Ageing prolongs inflammatory marker expression in regenerating rat skeletal muscles after injury","volume":"8","author":"Gosselin","year":"2011","journal-title":"J. Inflamm."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.mvr.2018.05.007","article-title":"Human cancer cells suppress behaviors of endothelial progenitor cells through miR-21 targeting IL6R","volume":"120","author":"Wang","year":"2018","journal-title":"Microvasc. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3148","DOI":"10.3390\/ijms16023148","article-title":"The Regulation and Function of miR-21-FOXO3a-miR-34b\/c Signaling in Breast Cancer","volume":"16","author":"Liu","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_44","first-page":"433","article-title":"MiR-21 inhibitor improves locomotor function recovery by inhibiting IL-6R\/JAK-STAT pathway-mediated inflammation after spinal cord injury in model of rat","volume":"23","author":"Ning","year":"2019","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1016\/j.cca.2010.02.074","article-title":"MicroRNA-21 (miR-21) represses tumor suppressor PTEN and promotes growth and invasion in non-small cell lung cancer (NSCLC)","volume":"411","author":"Zhang","year":"2010","journal-title":"Clin. Chim. Acta"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1186\/s12964-018-0268-4","article-title":"Activation of the JAK\/STAT3 and PI3K\/AKT pathways are crucial for IL-6 trans-signaling-mediated pro-inflammatory response in human vascular endothelial cells","volume":"16","author":"Zegeye","year":"2018","journal-title":"Cell Commun. Signal."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1055\/s-2007-970414","article-title":"Role of Tumor Suppressor PTEN in Tumor Necrosis Factor ?-Induced Inhibition of Insulin Signaling in Murine Skeletal Muscle C 2 C 12 Cells","volume":"39","author":"Lo","year":"2007","journal-title":"Horm. Metab. Res."},{"key":"ref_48","first-page":"267","article-title":"NF-kB and Inflammatory Cytokine Signalling: Role in Skeletal Muscle Atrophy","volume":"1088","author":"Thoma","year":"2018","journal-title":"Results Probl. Cell Differ."},{"key":"ref_49","first-page":"1764","article-title":"The functional analysis of MicroRNAs involved in NF-\u03baB signaling","volume":"20","author":"Yang","year":"2016","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1016\/j.freeradbiomed.2012.02.020","article-title":"Regulation of miRNA-21 by reactive oxygen species-activated ERK\/NF-\u03baB in arsenite-induced cell transformation","volume":"52","author":"Ling","year":"2012","journal-title":"Free Radic. Biol. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"167","DOI":"10.3389\/fgene.2020.00167","article-title":"Circulating MicroRNAs in Plasma Decrease in Response to Sarcopenia in the Elderly","volume":"11","author":"He","year":"2020","journal-title":"Front. Genet."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"87","DOI":"10.3389\/fphys.2020.00087","article-title":"Divergent Roles of Inflammation in Skeletal Muscle Recovery from Injury","volume":"11","author":"Howard","year":"2020","journal-title":"Front. Physiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1002\/jcp.10387","article-title":"Multifaceted roles of TNF-? in myoblast destruction: A multitude of signal transduction pathways","volume":"198","author":"Stewart","year":"2003","journal-title":"J. Cell. Physiol."},{"key":"ref_54","first-page":"618","article-title":"Effects of miR-21 on proliferation and apoptosis in human gastric adenocarcinoma cells","volume":"15","author":"Gu","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s10020-018-0034-5","article-title":"Overexpression of miR-21-5p promotes proliferation and invasion of colon adenocarcinoma cells through targeting CHL1","volume":"24","author":"Yu","year":"2018","journal-title":"Mol. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"200","DOI":"10.3382\/ps\/pew281","article-title":"Gga-miR-21 inhibits chicken pre-adipocyte proliferation in part by down-regulating Kruppel-like factor 5","volume":"96","author":"Wang","year":"2017","journal-title":"Poult. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1038\/emm.2007.14","article-title":"TNF-alpha upregulates PTEN via NF-kappaB signaling pathways in human leukemic cells","volume":"39","author":"Lee","year":"2007","journal-title":"Exp. Mol. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"4294","DOI":"10.1111\/febs.12253","article-title":"Mechanisms regulating skeletal muscle growth and atrophy","volume":"280","author":"Schiaffino","year":"2013","journal-title":"FEBS J."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2449","DOI":"10.2337\/db06-1731","article-title":"PTEN Expression Contributes to the Regulation of Muscle Protein Degradation in Diabetes","volume":"56","author":"Hu","year":"2007","journal-title":"Diabetes"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2340","DOI":"10.1016\/j.celrep.2016.11.002","article-title":"Conditional Loss of Pten in Myogenic Progenitors Leads to Postnatal Skeletal Muscle Hypertrophy but Age-Dependent Exhaustion of Satellite Cells","volume":"17","author":"Yue","year":"2016","journal-title":"Cell Rep."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"14328","DOI":"10.1038\/ncomms14328","article-title":"Pten is necessary for the quiescence and maintenance of adult muscle stem cells","volume":"8","author":"Yue","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1002\/jcsm.12043","article-title":"Skeletal muscle wasting in cachexia and sarcopenia: Molecular pathophysiology and impact of exercise training","volume":"6","author":"Bowen","year":"2015","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/S0092-8674(04)00400-3","article-title":"Foxo Transcription Factors Induce the Atrophy-Related Ubiquitin Ligase Atrogin-1 and Cause Skeletal Muscle Atrophy","volume":"117","author":"Sandri","year":"2004","journal-title":"Cell"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Fasano, C., Disciglio, V., Bertora, S., Signorile, M.L., and Simone, C. (2019). FOXO3a from the Nucleus to the Mitochondria: A Round Trip in Cellular Stress Response. Cells, 8.","DOI":"10.3390\/cells8091110"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"27290","DOI":"10.1074\/jbc.M112.374777","article-title":"Stress-induced Skeletal Muscle Gadd45a Expression Reprograms Myonuclei and Causes Muscle Atrophy*","volume":"287","author":"Ebert","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"17496","DOI":"10.1074\/jbc.M116.740308","article-title":"Gadd45a Protein Promotes Skeletal Muscle Atrophy by Forming a Complex with the Protein Kinase MEKK4*\u2666","volume":"291","author":"Bullard","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1186\/s40064-016-2197-2","article-title":"Skeletal muscle wasting and renewal: A pivotal role of myokine IL-6","volume":"5","author":"Borges","year":"2016","journal-title":"SpringerPlus"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1172\/JCI96462","article-title":"Ectopic upregulation of membrane-bound IL6R drives vascular remodeling in pulmonary arterial hypertension","volume":"128","author":"Tamura","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"18015","DOI":"10.1074\/jbc.W119.011598","article-title":"DNA damage induces NF-\u03baB-dependent microRNA-21 up-regulation and promotes breast cancer cell invasion","volume":"22","author":"Niu","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1159\/000341444","article-title":"Matrine inhibits breast cancer growth via miR-21\/PTEN\/Akt pathway in MCF-7 cells","volume":"30","author":"Li","year":"2012","journal-title":"Cell Physiol. Biochem."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/9\/4\/345\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:27:03Z","timestamp":1760365623000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/9\/4\/345"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,23]]},"references-count":70,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,4]]}},"alternative-id":["antiox9040345"],"URL":"https:\/\/doi.org\/10.3390\/antiox9040345","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,23]]}}}