{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T08:23:18Z","timestamp":1784622198152,"version":"3.55.0"},"reference-count":75,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,10,14]],"date-time":"2022-10-14T00:00:00Z","timestamp":1665705600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"United States Trotting Association"},{"name":"Grayson Jockey Club Research Foundation"},{"name":"Mary Anne McPhail Endowment at Michigan State University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Certain Standardbred racehorses develop recurrent exertional rhabdomyolysis (RER-STD) for unknown reasons. We compared gluteal muscle histopathology and gene\/protein expression between Standardbreds with a history of, but not currently experiencing rhabdomyolysis (N = 9), and race-trained controls (N = 7). Eight RER-STD had a few mature fibers with small internalized myonuclei, one out of nine had histologic evidence of regeneration and zero out of nine degeneration. However, RER-STD versus controls had 791\/13,531 differentially expressed genes (DEG). The top three gene ontology (GO) enriched pathways for upregulated DEG (N = 433) were inflammation\/immune response (62 GO terms), cell proliferation (31 GO terms), and hypoxia\/oxidative stress (31 GO terms). Calcium ion regulation (39 GO terms), purine nucleotide metabolism (32 GO terms), and electron transport (29 GO terms) were the top three enriched GO pathways for down-regulated DEG (N = 305). DEG regulated RYR1 and sarcoplasmic reticulum calcium stores. Differentially expressed proteins (DEP \u2191N = 50, \u2193N = 12) involved the sarcomere (24% of DEP), electron transport (23%), metabolism (20%), inflammation (6%), cell\/oxidative stress (7%), and other (17%). DEP included \u2191superoxide dismutase, \u2191catalase, and DEP\/DEG included several cysteine-based antioxidants. In conclusion, gluteal muscle of RER-susceptible Standardbreds is characterized by perturbation of pathways for calcium regulation, cellular\/oxidative stress, inflammation, and cellular regeneration weeks after an episode of rhabdomyolysis that could represent therapeutic targets.<\/jats:p>","DOI":"10.3390\/genes13101853","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T00:04:55Z","timestamp":1665965095000},"page":"1853","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Enriched Pathways of Calcium Regulation, Cellular\/Oxidative Stress, Inflammation, and Cell Proliferation Characterize Gluteal Muscle of Standardbred Horses between Episodes of Recurrent Exertional Rhabdomyolysis"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5978-7010","authenticated-orcid":false,"given":"Stephanie J.","family":"Valberg","sequence":"first","affiliation":[{"name":"Mary Anne McPhail Equine Performance Center, Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Velez-Irizarry","sequence":"additional","affiliation":[{"name":"Mary Anne McPhail Equine Performance Center, Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zo\u00eb J.","family":"Williams","sequence":"additional","affiliation":[{"name":"Mary Anne McPhail Equine Performance Center, Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marisa L.","family":"Henry","sequence":"additional","affiliation":[{"name":"Mary Anne McPhail Equine Performance Center, Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailey","family":"Iglewski","sequence":"additional","affiliation":[{"name":"Mary Anne McPhail Equine Performance Center, Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keely","family":"Herrick","sequence":"additional","affiliation":[{"name":"Mary Anne McPhail Equine Performance Center, Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6234-3197","authenticated-orcid":false,"given":"Clara","family":"Fenger","sequence":"additional","affiliation":[{"name":"Equine Integrated Medicine, PLC, Lexington, KY 40324, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Isgren, C.M., Upjohn, M.M., Fernandez-Fuente, M., Massey, C., Pollott, G., Verheyen, K.L., and Piercy, R.J. 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