Satellite cell activation and apoptosis in skeletal muscle from severely burned children

Christopher Fry, Craig Porter, Labros S. Sidossis, Christopher Nieten, Paul T. Reidy, Gabriel Hundeshagen, Ronald Mlcak, Blake Rasmussen, Jong Lee, Oscar Suman, David Herndon, Celeste Finnerty

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Key points: 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.

Original languageEnglish (US)
JournalJournal of Physiology
DOIs
StateAccepted/In press - 2016

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Skeletal Muscle
Apoptosis
Muscular Atrophy
Muscles
Burns
Wounds and Injuries
Regeneration
In Situ Nick-End Labeling
Muscle Cells
Survivors
Cachexia
Myosin Heavy Chains
Body Surface Area
Muscle Weakness
Quadriceps Muscle
Caspase 3
DNA Damage
Healthy Volunteers
Stem Cells
Immunohistochemistry

Keywords

  • Burn patients
  • MyoD
  • Pax7
  • Regeneration

ASJC Scopus subject areas

  • Physiology

Cite this

Satellite cell activation and apoptosis in skeletal muscle from severely burned children. / Fry, Christopher; Porter, Craig; Sidossis, Labros S.; Nieten, Christopher; Reidy, Paul T.; Hundeshagen, Gabriel; Mlcak, Ronald; Rasmussen, Blake; Lee, Jong; Suman, Oscar; Herndon, David; Finnerty, Celeste.

In: Journal of Physiology, 2016.

Research output: Contribution to journalArticle

Fry, Christopher ; Porter, Craig ; Sidossis, Labros S. ; Nieten, Christopher ; Reidy, Paul T. ; Hundeshagen, Gabriel ; Mlcak, Ronald ; Rasmussen, Blake ; Lee, Jong ; Suman, Oscar ; Herndon, David ; Finnerty, Celeste. / Satellite cell activation and apoptosis in skeletal muscle from severely burned children. In: Journal of Physiology. 2016.
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abstract = "Key points: 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.",
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AU - Fry, Christopher

AU - Porter, Craig

AU - Sidossis, Labros S.

AU - Nieten, Christopher

AU - Reidy, Paul T.

AU - Hundeshagen, Gabriel

AU - Mlcak, Ronald

AU - Rasmussen, Blake

AU - Lee, Jong

AU - Suman, Oscar

AU - Herndon, David

AU - Finnerty, Celeste

PY - 2016

Y1 - 2016

N2 - Key points: 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.

AB - Key points: 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.

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KW - Pax7

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