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. Abstract: 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 language | English |
|---|---|
| Pages (from-to) | 5223-5236 |
| Number of pages | 14 |
| Journal | Journal of Physiology |
| Volume | 594 |
| Issue number | 18 |
| DOIs | |
| State | Published - Sep 15 2016 |
Bibliographical note
Funding Information:This project was supported by a pilot grant from the UTMB Department of Surgery to C.S.F., O.E.S. and C.C.F. C.S.F. is a KL2 scholar supported by the UTMB Claude D. Pepper Older Americans Independence Center NIH/NIA grant P30 AG024832. This project was supported by grants from: the National Institutes of Health AG051267 to B.B.R., HD049471 to O.E.S., R01‐GM056687 and P50‐GM060338 to D.N.H., R01‐GM‐112936 to C.C.F.; from the National Institute on Disability, Independent Living, and Rehabilitation Research to D.N.H. (90DP0043‐01‐00); grants from the Anderson Foundation and the Gillson Longebaugh Foundation to D.N.H. and C.C.F.; and from the Shriners Hospitals for Children to D.N.H. (84080, 79141, 71008), O.E.S. (71009, 71006), and the Research Support Core (80100). The project was conducted with the support of UTMB's Institute for Translational Sciences, supported in part by a Clinical and Translational Science Award (UL1TR000071) from the National Center for Advancing Translational Sciences (NIH).
Publisher Copyright:
© 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society
Keywords
- MyoD
- Pax7
- burn patients
- regeneration
ASJC Scopus subject areas
- Physiology