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Metformin alleviates muscle wasting post-thermal injury by increasing Pax7-positive muscle progenitor cells

BACKGROUND: Profound skeletal muscle wasting and weakness is common after severe burn and persists for years after injury contributing to morbidity and mortality of burn patients. Currently, no ideal treatment exists to inhibit muscle catabolism. Metformin is an anti-diabetic agent that manages hype...

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Autores principales: Yousuf, Yusef, Datu, Andrea, Barnes, Ben, Amini-Nik, Saeid, Jeschke, Marc G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6950874/
https://www.ncbi.nlm.nih.gov/pubmed/31915055
http://dx.doi.org/10.1186/s13287-019-1480-x
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author Yousuf, Yusef
Datu, Andrea
Barnes, Ben
Amini-Nik, Saeid
Jeschke, Marc G.
author_facet Yousuf, Yusef
Datu, Andrea
Barnes, Ben
Amini-Nik, Saeid
Jeschke, Marc G.
author_sort Yousuf, Yusef
collection PubMed
description BACKGROUND: Profound skeletal muscle wasting and weakness is common after severe burn and persists for years after injury contributing to morbidity and mortality of burn patients. Currently, no ideal treatment exists to inhibit muscle catabolism. Metformin is an anti-diabetic agent that manages hyperglycemia but has also been shown to have a beneficial effect on stem cells after injury. We hypothesize that metformin administration will increase protein synthesis in the skeletal muscle by increasing the proliferation of muscle progenitor cells, thus mitigating muscle atrophy post-burn injury. METHODS: To determine whether metformin can attenuate muscle catabolism following burn injury, we utilized a 30% total burn surface area (TBSA) full-thickness scald burn in mice and compared burn injuries with and without metformin treatment. We examined the gastrocnemius muscle at 7 and 14 days post-burn injury. RESULTS: At 7 days, burn injury significantly reduced myofiber cross-sectional area (CSA) compared to sham, p < 0.05. Metformin treatment significantly attenuated muscle catabolism and preserved muscle CSA at the sham size. To investigate metformin’s effect on satellite cells (muscle progenitors), we examined changes in Pax7, a transcription factor regulating the proliferation of muscle progenitors. Burned animals treated with metformin had a significant increase in Pax7 protein level and the number of Pax7-positive cells at 7 days post-burn, p < 0.05. Moreover, through BrdU proliferation assay, we show that metformin treatment increased the proliferation of satellite cells at 7 days post-burn injury, p < 0.05. CONCLUSION: In summary, metformin’s various metabolic effects and its modulation of stem cells make it an attractive alternative to mitigate burn-induced muscle wasting while also managing hyperglycemia.
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spelling pubmed-69508742020-01-09 Metformin alleviates muscle wasting post-thermal injury by increasing Pax7-positive muscle progenitor cells Yousuf, Yusef Datu, Andrea Barnes, Ben Amini-Nik, Saeid Jeschke, Marc G. Stem Cell Res Ther Research BACKGROUND: Profound skeletal muscle wasting and weakness is common after severe burn and persists for years after injury contributing to morbidity and mortality of burn patients. Currently, no ideal treatment exists to inhibit muscle catabolism. Metformin is an anti-diabetic agent that manages hyperglycemia but has also been shown to have a beneficial effect on stem cells after injury. We hypothesize that metformin administration will increase protein synthesis in the skeletal muscle by increasing the proliferation of muscle progenitor cells, thus mitigating muscle atrophy post-burn injury. METHODS: To determine whether metformin can attenuate muscle catabolism following burn injury, we utilized a 30% total burn surface area (TBSA) full-thickness scald burn in mice and compared burn injuries with and without metformin treatment. We examined the gastrocnemius muscle at 7 and 14 days post-burn injury. RESULTS: At 7 days, burn injury significantly reduced myofiber cross-sectional area (CSA) compared to sham, p < 0.05. Metformin treatment significantly attenuated muscle catabolism and preserved muscle CSA at the sham size. To investigate metformin’s effect on satellite cells (muscle progenitors), we examined changes in Pax7, a transcription factor regulating the proliferation of muscle progenitors. Burned animals treated with metformin had a significant increase in Pax7 protein level and the number of Pax7-positive cells at 7 days post-burn, p < 0.05. Moreover, through BrdU proliferation assay, we show that metformin treatment increased the proliferation of satellite cells at 7 days post-burn injury, p < 0.05. CONCLUSION: In summary, metformin’s various metabolic effects and its modulation of stem cells make it an attractive alternative to mitigate burn-induced muscle wasting while also managing hyperglycemia. BioMed Central 2020-01-08 /pmc/articles/PMC6950874/ /pubmed/31915055 http://dx.doi.org/10.1186/s13287-019-1480-x Text en © The Author(s). 2020 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Yousuf, Yusef
Datu, Andrea
Barnes, Ben
Amini-Nik, Saeid
Jeschke, Marc G.
Metformin alleviates muscle wasting post-thermal injury by increasing Pax7-positive muscle progenitor cells
title Metformin alleviates muscle wasting post-thermal injury by increasing Pax7-positive muscle progenitor cells
title_full Metformin alleviates muscle wasting post-thermal injury by increasing Pax7-positive muscle progenitor cells
title_fullStr Metformin alleviates muscle wasting post-thermal injury by increasing Pax7-positive muscle progenitor cells
title_full_unstemmed Metformin alleviates muscle wasting post-thermal injury by increasing Pax7-positive muscle progenitor cells
title_short Metformin alleviates muscle wasting post-thermal injury by increasing Pax7-positive muscle progenitor cells
title_sort metformin alleviates muscle wasting post-thermal injury by increasing pax7-positive muscle progenitor cells
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6950874/
https://www.ncbi.nlm.nih.gov/pubmed/31915055
http://dx.doi.org/10.1186/s13287-019-1480-x
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