{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T05:56:50Z","timestamp":1790575010408,"version":"4.1.0"},"reference-count":68,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Physiological Reports"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Duchenne muscular dystrophy (DMD) is characterized by chronic skeletal muscle injury and degeneration. We discovered activation of protein kinase R (PKR; EIF2AK2), a regulator of the integrated stress response, in dystrophic muscle; however, its role in DMD remains unknown. We hypothesized that the PKR inhibitor imoxin (IMX) would improve muscle force and attenuate fibrosis, inflammatory signaling, and ER stress in diaphragms from mdx mice. C57 and mdx mice were treated with vehicle or IMX for ~24 wks (0.5\u2009mg\/kg, subcutaneous, 5 times\/wk). Specific force was decreased (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001), and dynamic passive force was increased (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.001) by disease, but there were no IMX effects. Disease\u2010increased fibrotic area was decreased by IMX (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.038); however, IMX failed to reduce fibronectin, collagen, or TGF\u2010\u03b21 signaling proteins. PKR and phosphorylated (p)PKR (thr446) were increased in mdx (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001) and maintained despite IMX treatment. Similarly, PKR regulators (total PACT, pPACT (ser18), TRBP, and PP1\u03b1), and PKR substrates (total eIF2\u03b1 and peIF2\u03b1 (ser51)) were also increased with disease (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001), but unaffected by IMX. Likewise, IMX did not attenuate disease\u2010mediated elevations in inflammatory signaling and ER stress markers. Overall, the dose of IMX was insufficient to attenuate PKR activation and failed to improve muscle function or prevent pathology in dystrophic skeletal muscle.\n                  <\/jats:p>","DOI":"10.14814\/phy2.71115","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T10:23:40Z","timestamp":1789986220000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Long\u2010term imoxin treatment does not attenuate disease severity in dystrophic diaphragm of male mice"],"prefix":"10.14814","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3908-2766","authenticated-orcid":false,"given":"Ji Heun","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Kinesiology Iowa State University  Ames Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgan E.","family":"Vorwald","sequence":"additional","affiliation":[{"name":"Department of Animal Science Iowa State University  Ames Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Roths","sequence":"additional","affiliation":[{"name":"Department of Animal Science Iowa State University  Ames Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3797-7539","authenticated-orcid":false,"given":"Joshua T.","family":"Selsby","sequence":"additional","affiliation":[{"name":"Department of Animal Science Iowa State University  Ames Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudy J.","family":"Valentine","sequence":"additional","affiliation":[{"name":"Department of Kinesiology Iowa State University  Ames Iowa USA"},{"name":"Department of Physical Therapy &amp; Kinesiology University of Massachusetts Lowell  Lowell Massachusetts 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