{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T13:37:27Z","timestamp":1783690647234,"version":"3.55.0"},"reference-count":36,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,5,23]],"date-time":"2021-05-23T00:00:00Z","timestamp":1621728000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Superoxide dismutase (SOD) is a major antioxidant enzyme for superoxide removal, and cytoplasmic SOD (SOD1) is expressed as a predominant isoform in all cells. We previously reported that renal SOD1 deficiency accelerates the progression of diabetic nephropathy (DN) via increasing renal oxidative stress. To evaluate whether the degree of SOD1 expression determines regeneration capacity and sarcopenic phenotypes of skeletal muscles under incipient and advanced DN conditions, we investigated the alterations of SOD1 expression, oxidative stress marker, inflammation, fibrosis, and regeneration capacity in cardiotoxin (CTX)-injured tibialis anterior (TA) muscles of two Akita diabetic mouse models with different susceptibility to DN, DN-resistant C57BL\/6-Ins2Akita and DN-prone KK\/Ta-Ins2Akita mice. Here, we report that KK\/Ta-Ins2Akita mice, but not C57BL\/6-Ins2Akita mice, exhibit delayed muscle regeneration after CTX injection, as demonstrated by the finding indicating significantly smaller average cross-sectional areas of regenerating TA muscle myofibers relative to KK\/Ta-wild-type mice. Furthermore, we observed markedly reduced SOD1 expression in CTX-injected TA muscles of KK\/Ta-Ins2Akita mice, but not C57BL\/6-Ins2Akita mice, along with increased inflammatory cell infiltration, prominent fibrosis and superoxide overproduction. Our study provides the first evidence that SOD1 reduction and the following superoxide overproduction delay skeletal muscle regeneration through induction of overt inflammation and fibrosis in a mouse model of progressive DN.<\/jats:p>","DOI":"10.3390\/ijms22115491","type":"journal-article","created":{"date-parts":[[2021,5,23]],"date-time":"2021-05-23T23:58:05Z","timestamp":1621814285000},"page":"5491","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Reduction of Superoxide Dismutase 1 Delays Regeneration of Cardiotoxin-Injured Skeletal Muscle in KK\/Ta-Ins2Akita Mice with Progressive Diabetic Nephropathy"],"prefix":"10.3390","volume":"22","author":[{"given":"Yuya","family":"Takahashi","sequence":"first","affiliation":[{"name":"Department of Metabolism and Endocrinology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsunori","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Department of Metabolism and Endocrinology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunsuke","family":"Kato","sequence":"additional","affiliation":[{"name":"Department of Metabolism and Endocrinology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7844-8564","authenticated-orcid":false,"given":"Mitsuhiko","family":"Nara","sequence":"additional","affiliation":[{"name":"Department of Metabolism and Endocrinology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumi","family":"Suganuma","sequence":"additional","affiliation":[{"name":"Department of Metabolism and Endocrinology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takehiro","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Metabolism and Endocrinology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsukasa","family":"Morii","sequence":"additional","affiliation":[{"name":"Department of Metabolism and Endocrinology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichiro","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Metabolism and Endocrinology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan"},{"name":"Kansai Electric Power Medical Research Institute, 2-1-7 Fukushima-ku, Osaka 553-0003, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Fujita","sequence":"additional","affiliation":[{"name":"Department of Metabolism and Endocrinology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1007\/s41999-019-00216-x","article-title":"Association between sarcopenia and diabetes: A systematic review and meta-analysis of observational studies","volume":"10","author":"Veronese","year":"2019","journal-title":"Eur. 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