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Growth differentiation factor‐15 is associated with muscle mass in chronic obstructive pulmonary disease and promotes muscle wasting in vivo

BACKGROUND: Loss of muscle mass is a co‐morbidity common to a range of chronic diseases including chronic obstructive pulmonary disease (COPD). Several systemic features of COPD including increased inflammatory signalling, oxidative stress, and hypoxia are known to increase the expression of growth...

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Autores principales: Patel, Mehul S., Lee, Jen, Baz, Manuel, Wells, Claire E., Bloch, Susannah, Lewis, Amy, Donaldson, Anna V., Garfield, Benjamin E., Hopkinson, Nicholas S., Natanek, Amanda, Man, William D‐C, Wells, Dominic J., Baker, Emma H., Polkey, Michael I., Kemp, Paul R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4864181/
https://www.ncbi.nlm.nih.gov/pubmed/27239406
http://dx.doi.org/10.1002/jcsm.12096
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author Patel, Mehul S.
Lee, Jen
Baz, Manuel
Wells, Claire E.
Bloch, Susannah
Lewis, Amy
Donaldson, Anna V.
Garfield, Benjamin E.
Hopkinson, Nicholas S.
Natanek, Amanda
Man, William D‐C
Wells, Dominic J.
Baker, Emma H.
Polkey, Michael I.
Kemp, Paul R.
author_facet Patel, Mehul S.
Lee, Jen
Baz, Manuel
Wells, Claire E.
Bloch, Susannah
Lewis, Amy
Donaldson, Anna V.
Garfield, Benjamin E.
Hopkinson, Nicholas S.
Natanek, Amanda
Man, William D‐C
Wells, Dominic J.
Baker, Emma H.
Polkey, Michael I.
Kemp, Paul R.
author_sort Patel, Mehul S.
collection PubMed
description BACKGROUND: Loss of muscle mass is a co‐morbidity common to a range of chronic diseases including chronic obstructive pulmonary disease (COPD). Several systemic features of COPD including increased inflammatory signalling, oxidative stress, and hypoxia are known to increase the expression of growth differentiation factor‐15 (GDF‐15), a protein associated with muscle wasting in other diseases. We therefore hypothesized that GDF‐15 may contribute to muscle wasting in COPD. METHODS: We determined the expression of GDF‐15 in the serum and muscle of patients with COPD and analysed the association of GDF‐15 expression with muscle mass and exercise performance. To determine whether GDF‐15 had a direct effect on muscle, we also determined the effect of increased GDF‐15 expression on the tibialis anterior of mice by electroporation. RESULTS: Growth differentiation factor‐15 was increased in the circulation and muscle of COPD patients compared with controls. Circulating GDF‐15 was inversely correlated with rectus femoris cross‐sectional area (P < 0.001) and exercise capacity (P < 0.001) in two separate cohorts of patients but was not associated with body mass index. GDF‐15 levels were associated with 8‐oxo‐dG in the circulation of patients consistent with a role for oxidative stress in the production of this protein. Local over‐expression of GDF‐15 in mice caused wasting of the tibialis anterior muscle that expressed it but not in the contralateral muscle suggesting a direct effect of GDF‐15 on muscle mass (P < 0.001). CONCLUSIONS: Together, the data suggest that GDF‐15 contributes to the loss of muscle mass in COPD.
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spelling pubmed-48641812016-05-27 Growth differentiation factor‐15 is associated with muscle mass in chronic obstructive pulmonary disease and promotes muscle wasting in vivo Patel, Mehul S. Lee, Jen Baz, Manuel Wells, Claire E. Bloch, Susannah Lewis, Amy Donaldson, Anna V. Garfield, Benjamin E. Hopkinson, Nicholas S. Natanek, Amanda Man, William D‐C Wells, Dominic J. Baker, Emma H. Polkey, Michael I. Kemp, Paul R. J Cachexia Sarcopenia Muscle Original Articles BACKGROUND: Loss of muscle mass is a co‐morbidity common to a range of chronic diseases including chronic obstructive pulmonary disease (COPD). Several systemic features of COPD including increased inflammatory signalling, oxidative stress, and hypoxia are known to increase the expression of growth differentiation factor‐15 (GDF‐15), a protein associated with muscle wasting in other diseases. We therefore hypothesized that GDF‐15 may contribute to muscle wasting in COPD. METHODS: We determined the expression of GDF‐15 in the serum and muscle of patients with COPD and analysed the association of GDF‐15 expression with muscle mass and exercise performance. To determine whether GDF‐15 had a direct effect on muscle, we also determined the effect of increased GDF‐15 expression on the tibialis anterior of mice by electroporation. RESULTS: Growth differentiation factor‐15 was increased in the circulation and muscle of COPD patients compared with controls. Circulating GDF‐15 was inversely correlated with rectus femoris cross‐sectional area (P < 0.001) and exercise capacity (P < 0.001) in two separate cohorts of patients but was not associated with body mass index. GDF‐15 levels were associated with 8‐oxo‐dG in the circulation of patients consistent with a role for oxidative stress in the production of this protein. Local over‐expression of GDF‐15 in mice caused wasting of the tibialis anterior muscle that expressed it but not in the contralateral muscle suggesting a direct effect of GDF‐15 on muscle mass (P < 0.001). CONCLUSIONS: Together, the data suggest that GDF‐15 contributes to the loss of muscle mass in COPD. John Wiley and Sons Inc. 2015-12-29 2016-09 /pmc/articles/PMC4864181/ /pubmed/27239406 http://dx.doi.org/10.1002/jcsm.12096 Text en © 2015 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society of Sarcopenia, Cachexia and Wasting Disorders This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Patel, Mehul S.
Lee, Jen
Baz, Manuel
Wells, Claire E.
Bloch, Susannah
Lewis, Amy
Donaldson, Anna V.
Garfield, Benjamin E.
Hopkinson, Nicholas S.
Natanek, Amanda
Man, William D‐C
Wells, Dominic J.
Baker, Emma H.
Polkey, Michael I.
Kemp, Paul R.
Growth differentiation factor‐15 is associated with muscle mass in chronic obstructive pulmonary disease and promotes muscle wasting in vivo
title Growth differentiation factor‐15 is associated with muscle mass in chronic obstructive pulmonary disease and promotes muscle wasting in vivo
title_full Growth differentiation factor‐15 is associated with muscle mass in chronic obstructive pulmonary disease and promotes muscle wasting in vivo
title_fullStr Growth differentiation factor‐15 is associated with muscle mass in chronic obstructive pulmonary disease and promotes muscle wasting in vivo
title_full_unstemmed Growth differentiation factor‐15 is associated with muscle mass in chronic obstructive pulmonary disease and promotes muscle wasting in vivo
title_short Growth differentiation factor‐15 is associated with muscle mass in chronic obstructive pulmonary disease and promotes muscle wasting in vivo
title_sort growth differentiation factor‐15 is associated with muscle mass in chronic obstructive pulmonary disease and promotes muscle wasting in vivo
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4864181/
https://www.ncbi.nlm.nih.gov/pubmed/27239406
http://dx.doi.org/10.1002/jcsm.12096
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