title: Satellite cell activation and apoptosis in skeletal muscle from severely burned children.
abstract: Severe burns result in profound skeletal muscle atrophy that hampers recovery. The activity of skeletal muscle stem cells, satellite cells, acutely following a severe burn is unknown and may contribute to the recovery of lean muscle. Severe burn injury induces skeletal muscle regeneration and myonuclear apoptosis. Satellite cells undergo concurrent apoptosis and activation acutely following a burn, with a net reduction in satellite cell content compared to healthy controls. The activation and apoptosis of satellite cells probably impacts the recovery of lean tissue following a severe burn, contributing to prolonged frailty in burn survivors.
  
  
  
  Severe burns result in profound skeletal muscle atrophy; persistent muscle loss and weakness are major complications that hamper recovery from burn injury. Many factors contribute to the erosion of muscle mass following burn trauma and we propose that an impaired muscle satellite cell response is key in the aetiology of burn-induced cachexia. Muscle biopsies from the m. vastus lateralis were obtained from 12 male pediatric burn patients (>30% total body surface area burn) and 12 young, healthy male subjects. Satellite cell content, activation and apoptosis were determined via immunohistochemistry, as were muscle fibre regeneration and myonuclear apoptosis. Embryonic myosin heavy chain expression and central nucleation, indices of skeletal muscle regeneration, were elevated in burn patients (P < 0.05). Myonuclear apoptosis, quantified by TUNEL positive myonuclei and cleaved caspase-3 positive myonuclei, was also elevated in burn patients (P < 0.05). Satellite cell content was reduced in burn patients, with approximately 20% of satellite cells positive for TUNEL staining, indicating DNA damage associated with apoptosis (P < 0.05). Additionally, a significant percentage of satellite cells in burn patients expressed Ki67, a marker for cellular proliferation (P < 0.05). Satellite cell activation was also observed in burn patients with increased expression of MyoD compared to healthy controls (P < 0.05). Robust skeletal muscle atrophy occurs after burn injury, even in muscles located distally to the site of injury. The activation and apoptosis of satellite cells probably impacts the recovery of lean tissue following a severe burn, contributing to prolonged frailty in burn survivors.
authors.affiliation: Department of Nutrition and Metabolism, University of Texas Medical Branch, Galveston, TX, USA.|Institute for Translational Sciences, University of Texas Medical Branch, Galveston, TX, USA.|Shriners Hospitals for Children, Galveston, TX, USA.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Fry
authors.affiliation: Department of Surgery, University of Texas Medical Branch, Galveston, TX, USA.|Institute for Translational Sciences, University of Texas Medical Branch, Galveston, TX, USA.|Shriners Hospitals for Children, Galveston, TX, USA.
authors.forename: Craig
authors.initials: C
authors.lastname: Porter
authors.affiliation: Department of Surgery, University of Texas Medical Branch, Galveston, TX, USA.|Institute for Translational Sciences, University of Texas Medical Branch, Galveston, TX, USA.|Shriners Hospitals for Children, Galveston, TX, USA.
authors.forename: Labros S
authors.initials: LS
authors.lastname: Sidossis
authors.affiliation: Department of Surgery, University of Texas Medical Branch, Galveston, TX, USA.|Shriners Hospitals for Children, Galveston, TX, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Nieten
authors.affiliation: Department of Nutrition and Metabolism, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Reidy
authors.affiliation: Department of Surgery, University of Texas Medical Branch, Galveston, TX, USA.|Shriners Hospitals for Children, Galveston, TX, USA.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Hundeshagen
authors.affiliation: Shriners Hospitals for Children, Galveston, TX, USA.
authors.forename: Ronald
authors.initials: R
authors.lastname: Mlcak
authors.affiliation: Department of Nutrition and Metabolism, University of Texas Medical Branch, Galveston, TX, USA.|Institute for Translational Sciences, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Blake B
authors.initials: BB
authors.lastname: Rasmussen
authors.affiliation: Department of Surgery, University of Texas Medical Branch, Galveston, TX, USA.|Institute for Translational Sciences, University of Texas Medical Branch, Galveston, TX, USA.|Shriners Hospitals for Children, Galveston, TX, USA.
authors.forename: Jong O
authors.initials: JO
authors.lastname: Lee
authors.affiliation: Department of Surgery, University of Texas Medical Branch, Galveston, TX, USA.|Shriners Hospitals for Children, Galveston, TX, USA.
authors.forename: Oscar E
authors.initials: OE
authors.lastname: Suman
authors.affiliation: Department of Surgery, University of Texas Medical Branch, Galveston, TX, USA.|Institute for Translational Sciences, University of Texas Medical Branch, Galveston, TX, USA.|Shriners Hospitals for Children, Galveston, TX, USA.
authors.forename: David N
authors.initials: DN
authors.lastname: Herndon
authors.affiliation: Department of Surgery, University of Texas Medical Branch, Galveston, TX, USA. ccfinner@utmb.edu.|Institute for Translational Sciences, University of Texas Medical Branch, Galveston, TX, USA. ccfinner@utmb.edu.|Shriners Hospitals for Children, Galveston, TX, USA. ccfinner@utmb.edu.
authors.forename: Celeste C
authors.initials: CC
authors.lastname: Finnerty
mesh_terms: D000293:Adolescent; D000328:Adult; D017209:Apoptosis; D002056:Burns / Q000378:metabolism / Q000503:physiopathology*; D053148:Caspase 3 / Q000378:metabolism; D002648:Child; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology*; D017570:MyoD Protein / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000378:metabolism; D051763:PAX7 Transcription Factor / Q000378:metabolism; D012038:Regeneration; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism / Q000502:physiology*; D055815:Young Adult
chemical_list: D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D051763:PAX7 Transcription Factor; C497321:PAX7 protein, human; D053148:Caspase 3; D018995:Myosin Heavy Chains
keywords: MyoD; Pax7; burn patients; regeneration