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An unintended side effect of <jats:styled-content style=\"fixed-case\">GC<\/jats:styled-content> therapy is the stimulation of skeletal muscle atrophy. Pathophysiological mechanisms responsible for <jats:styled-content style=\"fixed-case\">GC<\/jats:styled-content>\u2010induced skeletal muscle atrophy have been extensively investigated, and the ability to treat patients with <jats:styled-content style=\"fixed-case\">GC<\/jats:styled-content> without unintended muscle atrophy has yet to be realized. We have reported that a single, standard\u2010of\u2010care dose of Methylprednisolone increases in\u00a0vivo expression of <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010<jats:italic>\u03ba<\/jats:italic>B\u2010inducing kinase (<jats:styled-content style=\"fixed-case\">NIK<\/jats:styled-content>), an important upstream regulatory kinase controlling <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010<jats:italic>\u03ba<\/jats:italic>B activation, along with other key muscle catabolic regulators such as Atrogin\u20101 and Mu<jats:styled-content style=\"fixed-case\">RF<\/jats:styled-content>1 that induce skeletal muscle proteolysis. Here, we provide experimental evidence that overexpressing <jats:styled-content style=\"fixed-case\">NIK<\/jats:styled-content> by intramuscular injection of recombinant human <jats:styled-content style=\"fixed-case\">NIK<\/jats:styled-content> via adenoviral vector in mouse tibialis anterior muscle induces a 30% decrease in the average fiber cross\u2010sectional area that is associated with increases in <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> expression of skeletal muscle atrophy biomarkers Mu<jats:styled-content style=\"fixed-case\">RF<\/jats:styled-content>1, Atrogin\u20101, myostatin and Gadd45. A single injection of <jats:styled-content style=\"fixed-case\">GC<\/jats:styled-content> induced <jats:styled-content style=\"fixed-case\">NIK mRNA<\/jats:styled-content> and protein within 2\u00a0h, with the increased <jats:styled-content style=\"fixed-case\">NIK<\/jats:styled-content> localized to nuclear and sarcolemmal locations within muscle fibers. Daily <jats:styled-content style=\"fixed-case\">GC<\/jats:styled-content> injections induced skeletal muscle fore limb weakness as early as 3\u00a0days with similar atrophy of muscle fibers as observed with <jats:styled-content style=\"fixed-case\">NIK<\/jats:styled-content> overexpression. <jats:styled-content style=\"fixed-case\">NIK<\/jats:styled-content> overexpression in primary human skeletal muscle myotubes increased skeletal muscle atrophy biomarkers, while <jats:styled-content style=\"fixed-case\">NIK<\/jats:styled-content> knockdown significantly attenuated GC\u2010induced increases in <jats:styled-content style=\"fixed-case\">NIK<\/jats:styled-content> and Atrogin\u20101. These results suggest that <jats:styled-content style=\"fixed-case\">NIK<\/jats:styled-content> may be a novel, previously unrecognized mediator of <jats:styled-content style=\"fixed-case\">GC<\/jats:styled-content>\u2010induced skeletal muscle atrophy.<\/jats:p>","DOI":"10.14814\/phy2.13014","type":"journal-article","created":{"date-parts":[[2016,11,15]],"date-time":"2016-11-15T01:10:17Z","timestamp":1479172217000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Glucocorticoids increase skeletal muscle <scp>NF<\/scp>\u2010<i>\u03ba<\/i>B inducing kinase (<scp>NIK<\/scp>): links to muscle atrophy"],"prefix":"10.14814","volume":"4","author":[{"given":"Christopher S.","family":"Fry","sequence":"first","affiliation":[{"name":"Department of Nutrition and Metabolism The University of Texas Medical Branch (UTMB) Galveston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed Z.","family":"Nayeem","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Division of Endocrinology The University of Texas Medical Branch (UTMB) Galveston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgar L.","family":"Dillon","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Division of Endocrinology The University of Texas Medical Branch (UTMB) Galveston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Partha S.","family":"Sarkar","sequence":"additional","affiliation":[{"name":"Department of Neurology The University of Texas Medical Branch (UTMB) Galveston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Batbayar","family":"Tumurbaatar","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Division of Endocrinology The University of Texas Medical Branch (UTMB) Galveston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randall J.","family":"Urban","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Division of Endocrinology The University of Texas Medical Branch (UTMB) Galveston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Traver J.","family":"Wright","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Division of Endocrinology The University of Texas Medical Branch (UTMB) Galveston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melinda","family":"Sheffield\u2010Moore","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Division of Endocrinology The University of Texas Medical Branch (UTMB) Galveston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald G.","family":"Tilton","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Division of Endocrinology The University of Texas Medical Branch (UTMB) Galveston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjeev","family":"Choudhary","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Division of Endocrinology The University of Texas Medical Branch (UTMB) Galveston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,11,14]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1786"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-005-1579-7"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2011.150995"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI23763"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.15-270579"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.01224"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2010.03.019"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600391"},{"key":"e_1_2_7_10_1","first-page":"CD001046","article-title":"Steroids for acute spinal cord injury","volume":"1","author":"Bracken M. 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