{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T23:20:31Z","timestamp":1771456831727,"version":"3.50.1"},"reference-count":25,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,2]],"date-time":"2025-08-02T00:00:00Z","timestamp":1754092800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"USU Intramural Research grant","award":["PPG-ANE-80-3397"],"award-info":[{"award-number":["PPG-ANE-80-3397"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objective: Exertional rhabdomyolysis (ER) is primarily driven by mechanical stress on muscles during strenuous or unaccustomed exercise, often exacerbated by environmental factors like heat and dehydration. While the general cellular pathway involving energy depletion and calcium overload is understood in horse ER models, the underlying mechanisms specific to the ER are not universally known within humans. This study aimed to evaluate whether patients with ER exhibited transcriptional signatures that were significantly different from those of healthy individuals. Methods: This study utilized RNA sequencing on skeletal muscle samples from 19 human patients with ER history, collected at a minimum of six months after the most recent ER event, and eight healthy controls to investigate the transcriptomic landscape of ER. To identify any alterations in biological processes between the case and control groups, functional pathway analyses were conducted. Results: Functional pathway enrichment analyses of differentially expressed genes revealed strong suppression of mitochondrial function. This suppression included the \u201caerobic electron transport chain\u201d and \u201coxidative phosphorylation\u201d pathways, indicating impaired energy production. Conversely, there was an upregulation of genes associated with adhesion and extracellular matrix-related pathways, indicating active restoration of muscle function in ER cases. Conclusions: The study demonstrated that muscle tissue exhibited signs of suppressed mitochondrial function and increased extracellular matrix development. Both of these facilitate muscle recovery within several months after an ER episode.<\/jats:p>","DOI":"10.3390\/genes16080930","type":"journal-article","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T10:58:26Z","timestamp":1754564306000},"page":"930","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["RNA Sequencing on Muscle Biopsies from Exertional Rhabdomyolysis Patients Revealed Down-Regulation of Mitochondrial Function and Enhancement of Extracellular Matrix Composition"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1561-7711","authenticated-orcid":false,"given":"Mingqiang","family":"Ren","sequence":"first","affiliation":[{"name":"Consortium for Health and Military Performance, Department of Military and Emergency Medicine, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"},{"name":"Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9651-3737","authenticated-orcid":false,"given":"Luke P.","family":"Michaelson","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"},{"name":"Department of Veterans Affairs, Baltimore VA Medical Healthcare System, Baltimore, MD 21201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ognoon","family":"Mungunsukh","sequence":"additional","affiliation":[{"name":"Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, USA"},{"name":"Department of Anatomy, Physiology and Genetics, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4159-1391","authenticated-orcid":false,"given":"Peter","family":"Bedocs","sequence":"additional","affiliation":[{"name":"Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, USA"},{"name":"Department of Anesthesiology, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"},{"name":"Defense & Veterans Center for Integrative Pain Management, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liam","family":"Friel","sequence":"additional","affiliation":[{"name":"Consortium for Health and Military Performance, Department of Military and Emergency Medicine, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"},{"name":"Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3690-5409","authenticated-orcid":false,"given":"Kristen","family":"Cofer","sequence":"additional","affiliation":[{"name":"Consortium for Health and Military Performance, Department of Military and Emergency Medicine, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"},{"name":"Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7554-5254","authenticated-orcid":false,"given":"Carolyn E.","family":"Dartt","sequence":"additional","affiliation":[{"name":"Consortium for Health and Military Performance, Department of Military and Emergency Medicine, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"},{"name":"Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nyamkhishig","family":"Sambuughin","sequence":"additional","affiliation":[{"name":"Consortium for Health and Military Performance, Department of Military and Emergency Medicine, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"},{"name":"Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francis G.","family":"O\u2019Connor","sequence":"additional","affiliation":[{"name":"Consortium for Health and Military Performance, Department of Military and Emergency Medicine, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"105344","DOI":"10.1016\/j.nmd.2025.105344","article-title":"276th ENMC International Workshop: Recommendations on optimal diagnostic pathway and management strategy for patients with acute rhabdomyolysis worldwide. 15th-17th March 2024, Hoofddorp, The Netherlands","volume":"50","author":"Kruijt","year":"2025","journal-title":"Neuromuscul. Disord."},{"key":"ref_2","unstructured":"Goldman, L., and Cooney, K.A. (2023). Rhabdomyolysis. 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