{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:14:43Z","timestamp":1791227683573,"version":"4.1.0"},"reference-count":46,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2007,7]]},"abstract":"<jats:p> MicroRNAs are highly conserved, noncoding RNAs involved in posttranscriptional gene silencing. MicroRNAs have been shown to be involved in a range of biological processes, including myogenesis and muscle regeneration. The objective of this study was to test the hypothesis that microRNA expression is altered in dystrophic muscle, with the greatest change occurring, of the muscles examined, in the diaphragm. The expression of the muscle-enriched microRNAs was determined in the soleus, plantaris, and diaphragm muscles of control and dystrophin-deficient ( mdx) mice by semiquantitative PCR. In the soleus and plantaris, expression of the mature microRNA 133a (miR-133a) and miR-206, respectively, was decreased by \u223c25%, whereas in the diaphragm, miR-206 expression increased by 4.5-fold relative to control. The increased expression of miR-206 in the mdx diaphragm was paralleled by a 4.4-fold increase in primary miRNA-206 (pri-miRNA-206) transcript level. Expression of Myod1 was elevated 2.7-fold only in the mdx diaphragm, consistent with an earlier finding demonstrating Myod1 can activate pri-miRNA-206 transcription. Transcript levels of Drosha and Dicer, major components of microRNA biogenesis pathway, were unchanged in mdx muscle, suggesting the pathway is not altered under dystrophic conditions. Previous in vitro analysis found miR-206 was capable of repressing utrophin expression; however, under dystrophic conditions, both utrophin transcript and protein levels were significantly increased by 69% and 3.9-fold, respectively, a finding inconsistent with microRNA regulation. These results are the first to report alterations in expression of muscle-enriched microRNAs in skeletal muscle of the mdx mouse, suggesting microRNAs may have a role in the pathophysiology of muscular dystrophy. <\/jats:p>","DOI":"10.1152\/ajpcell.00077.2007","type":"journal-article","created":{"date-parts":[[2007,4,26]],"date-time":"2007-04-26T05:33:32Z","timestamp":1177565612000},"page":"C451-C457","source":"Crossref","is-referenced-by-count":101,"title":["MicroRNA-206 is overexpressed in the diaphragm but not the hindlimb muscle of mdx mouse"],"prefix":"10.1152","volume":"293","author":[{"given":"John J.","family":"McCarthy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karyn A.","family":"Esser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco H.","family":"Andrade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"crossref","unstructured":"Anderson JE, McIntosh LM, Moor AN, Yablonka-Reuveni Z. Levels of MyoD protein expression following injury of mdx and normal limb muscle are modified by thyroid hormone. J Histochem Cytochem 46: 59\u201367, 1998.","DOI":"10.1177\/002215549804600108"},{"key":"R2","doi-asserted-by":"crossref","unstructured":"Angus LM, Chakkalakal JV, Mejat A, Eibl JK, Belanger G, Megeney LA, Chin ER, Schaeffer L, Michel RN, Jasmin BJ. Calcineurin-NFAT signaling, together with GABP and peroxisome PGC-1\u03b1, drives utrophin gene expression at the neuromuscular junction. Am J Physiol Cell Physiol 289: C908\u2013C917, 2005.","DOI":"10.1152\/ajpcell.00196.2005"},{"key":"R3","doi-asserted-by":"crossref","unstructured":"Bhattacharyya SN, Habermacher R, Martine U, Closs EI, Filipowicz W. Relief of microRNA-mediated translational repression in human cells subjected to stress. Cell 125: 1111\u20131124, 2006.","DOI":"10.1016\/j.cell.2006.04.031"},{"key":"R4","doi-asserted-by":"crossref","unstructured":"Blake DJ, Weir A, Newey SE, Davies KE. Function and genetics of dystrophin and dystrophin-related proteins in muscle. Physiol Rev 82: 291\u2013329, 2002.","DOI":"10.1152\/physrev.00028.2001"},{"key":"R5","doi-asserted-by":"crossref","unstructured":"Boland B, Himpens B, Denef JF, Gillis JM. Site-dependent pathological differences in smooth muscles and skeletal muscles of the adult mdx mouse. Muscle Nerve 18: 649\u2013657, 1995.","DOI":"10.1002\/mus.880180612"},{"key":"R6","doi-asserted-by":"crossref","unstructured":"Cai X, Hagedorn CH, Cullen BR. Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. RNA 10: 1957\u20131966, 2004.","DOI":"10.1261\/rna.7135204"},{"key":"R7","doi-asserted-by":"crossref","unstructured":"Campbell KP, Stull JT. Skeletal muscle basement membrane-sarcolemma-cytoskeleton interaction minireview series. J Biol Chem 278: 12599\u201312600, 2003.","DOI":"10.1074\/jbc.R300005200"},{"key":"R8","doi-asserted-by":"crossref","unstructured":"Carlson CG, Roshek DM. Adult dystrophic (mdx) endplates exhibit reduced quantal size and enhanced quantal variation. Pfl\u00fcgers Arch 442: 369\u2013375, 2001.","DOI":"10.1007\/s004240100561"},{"key":"R9","doi-asserted-by":"crossref","unstructured":"Carthew RW. Gene regulation by microRNAs. Curr Opin Genet Dev 16: 203\u2013208, 2006.","DOI":"10.1016\/j.gde.2006.02.012"},{"key":"R10","doi-asserted-by":"crossref","unstructured":"Chen JF, Mandel EM, Thomson JM, Wu Q, Callis TE, Hammond SM, Conlon FL, Wang DZ. The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation. Nat Genet 38: 228\u2013233, 2006.","DOI":"10.1038\/ng1725"},{"key":"R11","doi-asserted-by":"crossref","unstructured":"Doran P, Martin G, Dowling P, Jockusch H, Ohlendieck K. Proteome analysis of the dystrophin-deficient MDX diaphragm reveals a drastic increase in the heat shock protein cvHSP. Proteomics 6: 4610\u20134621, 2006.","DOI":"10.1002\/pmic.200600082"},{"key":"R12","doi-asserted-by":"crossref","unstructured":"Dupont-Versteegden EE, McCarter RJ. Differential expression of muscular dystrophy in diaphragm versus hindlimb muscles of mdx mice. Muscle Nerve 15: 1105\u20131110, 1992.","DOI":"10.1002\/mus.880151008"},{"key":"R13","doi-asserted-by":"crossref","unstructured":"Durbeej M, Campbell KP. Muscular dystrophies involving the dystrophin-glycoprotein complex: an overview of current mouse models. Curr Opin Genet Dev 12: 349\u2013361, 2002.","DOI":"10.1016\/S0959-437X(02)00309-X"},{"key":"R14","doi-asserted-by":"crossref","unstructured":"Even PC, Decrouy A, Chinet A. Defective regulation of energy metabolism in mdx-mouse skeletal muscles. Biochem J 304: 649\u2013654, 1994.","DOI":"10.1042\/bj3040649"},{"key":"R15","doi-asserted-by":"crossref","unstructured":"Gramolini AO, Belanger G, Jasmin BJ. Distinct regions in the 3\u2032 untranslated region are responsible for targeting and stabilizing utrophin transcripts in skeletal muscle cells. J Cell Biol 154: 1173\u20131183, 2001.","DOI":"10.1083\/jcb.200101108"},{"key":"R16","doi-asserted-by":"crossref","unstructured":"Harfe BD, McManus MT, Mansfield JH, Hornstein E, Tabin CJ. The RNaseIII enzyme Dicer is required for morphogenesis but not patterning of the vertebrate limb. Proc Natl Acad Sci USA 102: 10898\u201310903, 2005.","DOI":"10.1073\/pnas.0504834102"},{"key":"R17","doi-asserted-by":"crossref","unstructured":"Haslett JN, Kunkel LM. Microarray analysis of normal and dystrophic skeletal muscle. Int J Dev Neurosci 20: 359\u2013365, 2002.","DOI":"10.1016\/S0736-5748(02)00041-2"},{"key":"R18","doi-asserted-by":"crossref","unstructured":"Jackson RJ, Standart N. How do microRNAs regulate gene expression? Sci STKE 2007: re1, 2007.","DOI":"10.1126\/stke.3672007re1"},{"key":"R19","doi-asserted-by":"crossref","unstructured":"Kim HK, Lee YS, Sivaprasad U, Malhotra A, Dutta A. Muscle-specific microRNA miR-206 promotes muscle differentiation. J Cell Biol 174: 677\u2013687, 2006.","DOI":"10.1083\/jcb.200603008"},{"key":"R20","doi-asserted-by":"crossref","unstructured":"Kloosterman WP, Plasterk RH. The diverse functions of microRNAs in animal development and disease. Dev Cell 11: 441\u2013450, 2006.","DOI":"10.1016\/j.devcel.2006.09.009"},{"key":"R21","doi-asserted-by":"crossref","unstructured":"Kwon C, Han Z, Olson EN, Srivastava D. MicroRNA1 influences cardiac differentiation in Drosophila and regulates Notch signaling. Proc Natl Acad Sci USA 102: 18986\u201318991, 2005.","DOI":"10.1073\/pnas.0509535102"},{"key":"R22","doi-asserted-by":"crossref","unstructured":"Lee Y, Jeon K, Lee JT, Kim S, Kim VN. MicroRNA maturation: stepwise processing and subcellular localization. EMBO J 21: 4663\u20134670, 2002.","DOI":"10.1093\/emboj\/cdf476"},{"key":"R23","doi-asserted-by":"crossref","unstructured":"Louboutin JP, Fichter-Gagnepain V, Thaon E, Fardeau M. Morphometric analysis of mdx diaphragm muscle fibres. Comparison with hindlimb muscles. Neuromuscul Disord 3: 463\u2013469, 1993.","DOI":"10.1016\/0960-8966(93)90098-5"},{"key":"R24","doi-asserted-by":"crossref","unstructured":"McCarthy JJ, Esser KA. MicroRNA-1 and microRNA-133a expression are decreased during skeletal muscle hypertrophy. J Appl Physiol 102: 306\u2013313, 2007.","DOI":"10.1152\/japplphysiol.00932.2006"},{"key":"R25","doi-asserted-by":"crossref","unstructured":"Miranda KC, Huynh T, Tay Y, Ang YS, Tam WL, Thomson AM, Lim B, Rigoutsos I. A pattern-based method for the identification of MicroRNA binding sites and their corresponding heteroduplexes. Cell 126: 1203\u20131217, 2006.","DOI":"10.1016\/j.cell.2006.07.031"},{"key":"R26","doi-asserted-by":"crossref","unstructured":"Naguibneva I, Ameyar-Zazoua M, Polesskaya A, Ait-Si-Ali S, Groisman R, Souidi M, Cuvellier S, Harel-Bellan A. The microRNA miR-181 targets the homeobox protein Hox-A11 during mammalian myoblast differentiation. Nat Cell Biol 8: 278\u2013284, 2006.","DOI":"10.1038\/ncb1373"},{"key":"R27","doi-asserted-by":"crossref","unstructured":"Nguyen TM, Ellis JM, Love DR, Davies KE, Gatter KC, Dickson G, Morris GE. Localization of the DMDL gene-encoded dystrophin-related protein using a panel of nineteen monoclonal antibodies: presence at neuromuscular junctions, in the sarcolemma of dystrophic skeletal muscle, in vascular and other smooth muscles, and in proliferating brain cell lines. J Cell Biol 115: 1695\u20131700, 1991.","DOI":"10.1083\/jcb.115.6.1695"},{"key":"R28","doi-asserted-by":"crossref","unstructured":"Personius KE, Sawyer RP. Terminal Schwann cell structure is altered in diaphragm of mdx mice. Muscle Nerve 32: 656\u2013663, 2005.","DOI":"10.1002\/mus.20405"},{"key":"R29","doi-asserted-by":"crossref","unstructured":"Personius KE, Sawyer RP. Variability and failure of neurotransmission in the diaphragm of mdx mice. Neuromuscul Disord 16: 168\u2013177, 2006.","DOI":"10.1016\/j.nmd.2006.01.002"},{"key":"R30","doi-asserted-by":"crossref","unstructured":"Porter JD, Khanna S, Kaminski HJ, Rao JS, Merriam AP, Richmonds CR, Leahy P, Li J, Guo W, Andrade FH. A chronic inflammatory response dominates the skeletal muscle molecular signature in dystrophin-deficient mdx mice. Hum Mol Genet 11: 263\u2013272, 2002.","DOI":"10.1093\/hmg\/11.3.263"},{"key":"R31","doi-asserted-by":"crossref","unstructured":"Porter JD, Merriam AP, Leahy P, Gong B, Feuerman J, Cheng G, Khanna S. Temporal gene expression profiling of dystrophin-deficient (mdx) mouse diaphragm identifies conserved and muscle group-specific mechanisms in the pathogenesis of muscular dystrophy. Hum Mol Genet 13: 257\u2013269, 2004.","DOI":"10.1093\/hmg\/ddh033"},{"key":"R32","doi-asserted-by":"crossref","unstructured":"Porter JD, Merriam AP, Leahy P, Gong B, Khanna S. Dissection of temporal gene expression signatures of affected and spared muscle groups in dystrophin-deficient (mdx) mice. Hum Mol Genet 12: 1813\u20131821, 2003.","DOI":"10.1093\/hmg\/ddg197"},{"key":"R33","doi-asserted-by":"crossref","unstructured":"Rando TA, Disatnik MH, Yu Y, Franco A. Muscle cells from mdx mice have an increased susceptibility to oxidative stress. Neuromuscul Disord 8: 14\u201321, 1998.","DOI":"10.1016\/S0960-8966(97)00124-7"},{"key":"R34","doi-asserted-by":"crossref","unstructured":"Rao PK, Kumar RM, Farkhondeh M, Baskerville S, Lodish HF. Myogenic factors that regulate expression of muscle-specific microRNAs. Proc Natl Acad Sci USA 103: 8721\u20138726, 2006.","DOI":"10.1073\/pnas.0602831103"},{"key":"R35","doi-asserted-by":"crossref","unstructured":"Rodriguez A, Griffiths-Jones S, Ashurst JL, Bradley A. Identification of mammalian microRNA host genes and transcription units. Genome Res 14: 1902\u20131910, 2004.","DOI":"10.1101\/gr.2722704"},{"key":"R36","doi-asserted-by":"crossref","unstructured":"Rosenberg MI, Georges SA, Asawachaicharn A, Analau E, Tapscott SJ. MyoD inhibits Fstl1 and Utrn expression by inducing transcription of miR-206. J Cell Biol 175: 77\u201385, 2006.","DOI":"10.1083\/jcb.200603039"},{"key":"R37","doi-asserted-by":"crossref","unstructured":"Rouger K, Le Cunff M, Steenman M, Potier MC, Gibelin N, Dechesne CA, Leger JJ. Global\/temporal gene expression in diaphragm and hindlimb muscles of dystrophin-deficient (mdx) mice. Am J Physiol Cell Physiol 283: C773\u2013C784, 2002.","DOI":"10.1152\/ajpcell.00112.2002"},{"key":"R38","doi-asserted-by":"crossref","unstructured":"Stedman HH, Sweeney HL, Shrager JB, Maguire HC, Panettieri RA, Petrof B, Narusawa M, Leferovich JM, Sladky JT, Kelly AM. The mdx mouse diaphragm reproduces the degenerative changes of Duchenne muscular dystrophy. Nature 352: 536\u2013539, 1991.","DOI":"10.1038\/352536a0"},{"key":"R39","doi-asserted-by":"crossref","unstructured":"Tkatchenko AV, Le Cam G, Leger JJ, Dechesne CA. Large-scale analysis of differential gene expression in the hindlimb muscles and diaphragm of mdx mouse. Biochim Biophys Acta 1500: 17\u201330, 2000.","DOI":"10.1016\/S0925-4439(99)00084-8"},{"key":"R40","doi-asserted-by":"crossref","unstructured":"Turk R, Sterrenburg E, van der Wees CG, de Meijer EJ, de Menezes RX, Groh S, Campbell KP, Noguchi S, van Ommen GJ, den Dunnen JT, t'Hoen PA. Common pathological mechanisms in mouse models for muscular dystrophies. FASEB J 20: 127\u2013129, 2006.","DOI":"10.1096\/fj.05-4678fje"},{"key":"R41","doi-asserted-by":"crossref","unstructured":"van Rooij E, Sutherland LB, Liu N, Williams AH, McAnally J, Gerard RD, Richardson JA, Olson EN. A signature pattern of stress-responsive microRNAs that can evoke cardiac hypertrophy and heart failure. Proc Natl Acad Sci USA 103: 18255\u201318260, 2006.","DOI":"10.1073\/pnas.0608791103"},{"key":"R42","doi-asserted-by":"crossref","unstructured":"Velleca MA, Wallace MC, Merlie JP. A novel synapse-associated noncoding RNA. Mol Cell Biol 14: 7095\u20137104, 1994.","DOI":"10.1128\/MCB.14.11.7095"},{"key":"R43","doi-asserted-by":"crossref","unstructured":"Weir AP, Burton EA, Harrod G, Davies KE. A- and B-utrophin have different expression patterns and are differentially up-regulated in mdx muscle. J Biol Chem 277: 45285\u201345290, 2002.","DOI":"10.1074\/jbc.M205177200"},{"key":"R44","doi-asserted-by":"crossref","unstructured":"Wienholds E, Koudijs MJ, van Eeden FJ, Cuppen E, Plasterk RH. The microRNA-producing enzyme Dicer1 is essential for zebrafish development. Nat Genet 35: 217\u2013218, 2003.","DOI":"10.1038\/ng1251"},{"key":"R45","doi-asserted-by":"crossref","unstructured":"Yablonka-Reuveni Z, Anderson JE. Satellite cells from dystrophic (mdx) mice display accelerated differentiation in primary cultures and in isolated myofibers. Dev Dyn 235: 203\u2013212, 2006.","DOI":"10.1002\/dvdy.20602"},{"key":"R46","doi-asserted-by":"crossref","unstructured":"Zhao Y, Samal E, Srivastava D. Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis. Nature 436: 214\u2013220, 2005.","DOI":"10.1038\/nature03817"}],"container-title":["American Journal of Physiology-Cell Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.physiology.org\/doi\/pdf\/10.1152\/ajpcell.00077.2007","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T17:49:22Z","timestamp":1718646562000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.physiology.org\/doi\/10.1152\/ajpcell.00077.2007"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,7]]},"references-count":46,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2007,7]]}},"alternative-id":["10.1152\/ajpcell.00077.2007"],"URL":"https:\/\/doi.org\/10.1152\/ajpcell.00077.2007","relation":{},"ISSN":["0363-6143","1522-1563"],"issn-type":[{"value":"0363-6143","type":"print"},{"value":"1522-1563","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,7]]}}}