Key points: Severe burns result in significant skeletal muscle cachexia that impedes recovery. Activity of satellite cells, skeletal muscle stem cells, is altered following a burn injury and likely hinders regrowth of muscle. Severe burn injury induces satellite cell proliferation and fusion into myofibres with greater activity in muscles proximal to the injury site. Conditional depletion of satellite cells attenuates recovery of myofibre area and volume following a scald burn injury in mice. Skeletal muscle regrowth following a burn injury requires satellite cell activity, underscoring the therapeutic potential of satellite cells in the prevention of prolonged frailty in burn survivors. Abstract: Severe burns result in profound skeletal muscle atrophy; persistent muscle atrophy 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 have previously shown concurrent activation and apoptosis of muscle satellite cells following a burn injury in paediatric patients. To determine the necessity of satellite cells during muscle recovery following a burn injury, we utilized a genetically modified mouse model (Pax7CreER-DTA) that allows for the conditional depletion of satellite cells in skeletal muscle. Additionally, mice were provided 5-ethynyl-2′-deoxyuridine to determine satellite cell proliferation, activation and fusion. Juvenile satellite cell-wild-type (SC-WT) and satellite cell-depleted (SC-Dep) mice (8 weeks of age) were randomized to sham or burn injury consisting of a dorsal scald burn injury covering 30% of total body surface area. Both hindlimb and dorsal muscles were studied at 7, 14 and 21 days post-burn. SC-Dep mice had >93% depletion of satellite cells compared to SC-WT (P < 0.05). Burn injury induced robust atrophy in muscles located both proximal and distal to the injury site (∼30% decrease in fibre cross-sectional area, P < 0.05). Additionally, burn injury induced skeletal muscle regeneration, satellite cell proliferation and fusion. Depletion of satellite cells impaired post-burn recovery of both muscle fibre cross-sectional area and volume (P < 0.05). These findings support an integral role for satellite cells in the aetiology of lean tissue recovery following a severe burn injury.
|Number of pages||15|
|Journal||Journal of Physiology|
|State||Published - Nov 1 2017|
Bibliographical noteFunding 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 Centre NIH/NIA grant P30 AG024832. This project was supported by grants from: the National Institutes for Health HD049471 to O.E.S., GM56687 and GM60338 to D.N.H., GM112936 to C.C.F.; from the National Institute for 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 and 80500). 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 Centre for Advancing Translational Sciences (NIH).
© 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society
- scald injury
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