Original Articles
Activation of Satellite Cells in the Intercostal Muscles of Patients With Chronic Obstructive Pulmonary Disease
Juana Martínez-Llorensa,b, Carme Casadevallb, Josep Lloretaa,c,d, Mauricio Orozco-Levia,b,d, Esther Barreiroa,b,d, Joan Broquetasa,b,e, Joaquim Geaa,b,d,
Corresponding author
jgea@imim.es
Correspondence: Dr J. Gea Servei de Pneumologia, Hospital del Mar-IMIM Pg. Marítim, 25-27 08003 Barcelona, Spain
Correspondence: Dr J. Gea Servei de Pneumologia, Hospital del Mar-IMIM Pg. Marítim, 25-27 08003 Barcelona, Spain
a Servei de Pneumologia, Hospital del Mar-IMIM, Barcelona, Spain
b Unitat de Recerca en Múscul i Aparell Respiratori (URMAR), Hospital del Mar-IMIM, Barcelona, Spain
c Departament de Patologia, Hospital del Mar-IMIM, Barcelona, Spain
d Universitat Pompeu Fabra, CIBER de Enfermedades Respiratorias (CibeRes), Barcelona, Spain
e Universitat Autònoma de Barcelona, CIBER de Enfermedades Respiratorias (CibeRes), Barcelona, Spain
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"Universitat Pompeu Fabra, CIBER de Enfermedades Respiratorias (CibeRes), Barcelona, Spain" "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff4" ] 4 => array:3 [ "entidad" => "Universitat Autònoma de Barcelona, CIBER de Enfermedades Respiratorias (CibeRes), Barcelona, Spain" "etiqueta" => "<span class="elsevierStyleSup">e</span>" "identificador" => "aff5" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor1" "etiqueta" => "*" "correspondencia" => "Correspondence: Dr J. Gea Servei de Pneumologia, Hospital del Mar-IMIM Pg. Marítim, 25-27 08003 Barcelona, Spain" ] ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2007-05-15" "fechaAceptado" => "2007-11-20" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Key words" "identificador" => "xpalclavsec155239" "palabras" => array:5 [ 0 => "COPD" 1 => "Muscle dysfunction" 2 => "Damage" 3 => "Repair" 4 => "Satellite cells" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec155238" "palabras" => array:5 [ 0 => "EPOC" 1 => "Disfunción muscular" 2 => "Daño" 3 => "Reparación" 4 => "Células satélite" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:1 [ "resumen" => "<span class="elsevierStyleSectionTitle">Objective</span><p class="elsevierStyleSimplePara elsevierViewall">The respiratory muscles of patients with chronic obstructive pulmonary disease (COPD) display evidence of structural damage in parallel with signs of adaptation. We hypothesized that this can only be explained by the simultaneous activation of satellite cells. The aim of this study was to analyze the number and activation of those cells along with the expression of markers of microstructural damage that are frequently associated with regeneration.</p> <span class="elsevierStyleSectionTitle">Patients and methods</span><p class="elsevierStyleSimplePara elsevierViewall">The study included 8 patients with severe COPD (mean [SD] forced expiratory volume in 1 second, 33% [9%] of predicted) and 7 control subjects in whom biopsies were performed of the external intercostal muscle. The samples were analyzed by light microscopy to assess muscle fiber phenotype, electron microscopy to identify satellite cells, and real-time polymerase chain reaction to analyze the expression of the following markers: insulin-like growth factor 1, mechano growth factor, and embryonic and perinatal myosin heavy chains (MHC) as markers of microstructural damage; Pax-7 and m-cadherin as markers of the presence and activation of satellite cells, respectively; and MHC-I, IIa, and IIx as determinants of muscle fiber phenotype.</p> <span class="elsevierStyleSectionTitle">Results</span><p class="elsevierStyleSimplePara elsevierViewall">The patients had larger fibers than healthy subjects (54 [6] vs 42 [4] μm<span class="elsevierStyleSup">2</span>; <span class="elsevierStyleItalic">P</span> < .01) with a similar or slightly increased proportion of satellite cells, as measured by ultrastructural analysis (4.3% [1%] vs 3.7% [3.5%]; <span class="elsevierStyleItalic">P</span> > .05) or expression of Pax-7 (5.5 [4.1] vs 1.6 [0.8] arbitrary units [AU]; <span class="elsevierStyleItalic">P</span> < .05). In addition, there was greater activation of satellite cells in the patients, as indicated by increased expression of m-cadherin (3.8 [2.1] vs 1.0 [1.2] AU; <span class="elsevierStyleItalic">P</span>=.05). This was associated with increased expression of markers of microstructural damage: insulin-like growth factor 1, 0.35 (0.34) vs 0.09 (0.08) AU (<span class="elsevierStyleItalic">P</span> < .05); mechano growth factor, 0.45 (0.55) vs 0.13 (0.17) AU (<span class="elsevierStyleItalic">P</span>=.05). CONCLUSIONS: The intercostal muscles of patients with severe COPD show indirect signs of microstructural damage accompanied by satellite cell activation. This suggests the presence of ongoing cycles of lesion and repair that could partially explain the maintenance of the structural properties of the muscle.</p>" ] "es" => array:1 [ "resumen" => "<span class="elsevierStyleSectionTitle">Objetivo</span><p class="elsevierStyleSimplePara elsevierViewall">Los músculos respiratorios de los pacientes con enfermedad pulmonar obstructiva crónica (EPOC) presentan lesiones estructurales, que coexisten con signos de adaptación. Nuestra hipótesis es que esto sólo puede explicarse si se produce simultáneamente la activación de sus células satélite. El propósito del presente trabajo ha sido valorar el número y la eventual activación de dichas células, así como la expresión de marcadores de microlesión estructural, ligados a la regeneración.</p> <span class="elsevierStyleSectionTitle">Pacientes y métodos</span><p class="elsevierStyleSimplePara elsevierViewall">Se incluyó en el estudio a 8 pacientes con EPOC grave -media ± desviación estándar del volumen espiratorio forzado en el primer segundo: un 33 ± 9% del valor de referencia-y a 7 controles, a quienes se realizó una biopsia del músculo intercostal externo. La muestra se analizó mediante microscopia óptica (fenotipo fibrilar), electrónica (células satélite) y técnica de reacción en cadena de la polimerasa <span class="elsevierStyleItalic">en tiempo real</span> (marcadores de microlesión: factor de crecimiento similar a la insulina de tipo 1, factor de crecimiento mecánico e isoformas de cadenas pesadas de miosina [MyHC] embrionaria e isoformas de perinatal; de presencia y activación de células satélite: Pax-7 y m-caderina, respectivamente; y condicionantes del fenotipo fibrilar: MyHC-I, IIa y IIx).</p> <span class="elsevierStyleSectionTitle">Resultados</span><p class="elsevierStyleSimplePara elsevierViewall">Los pacientes tuvieron unas fibras mayores que los sujetos sanos (54 ± 6 frente a 42 ± 4 |a, m<span class="elsevierStyleSup">2</span>; p < 0,01), con una población de células satélite conservada o ligeramente incrementada (cuantificación ultraestructural: 4,3 ± 1% frente al 3,7 ± 3,5%, p no significativa; Pax-7: 5,5 ± 4,1 frente a 1,6 ± 0,8, unidades arbitrarias [ua], respectivamente, p < 0,05) y una mayor activación (m-caderina: 3,8 ± 2,1 frente a 1,0 ± 1,2 ua; p = 0,05). Esto se asociaba a valores aumentados de marcadores de microlesión (factor de crecimiento similar a la insulina de tipo 1: 0,35 ± 0,34 frente a 0,09 ± 0,08 ua, p < 0,05; factor de crecimiento mecánico: 0,45 ± 0,55 frente a 0,13 ± 0,17 ua, p = 0,05).</p> <span class="elsevierStyleSectionTitle">Conclusiones</span><p class="elsevierStyleSimplePara elsevierViewall">Los músculos intercostales de pacientes con EPOC grave muestran signos indirectos de microlesión, acompañados de la activación de sus células satélite. Esto apunta a la presencia de ciclos continuados de lesión y reparación, lo que podría explicar parcialmente la conservación de sus propiedades estructurales.</p>" ] ] "NotaPie" => array:1 [ 0 => array:1 [ "nota" => "<p class="elsevierStyleNotepara">This study was supported by funds from the European Union (Fifth Framework Programme, reference QLRT-2000-00417), the Spanish Ministry of Science and Technology (National R+D Plan, reference SAF 2001-0426), the Spanish Ministry of Health (Red RESPIRA, reference RTIC C03/11, Health Research Fund, Carlos III Health Institute), the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR), and the Generalitat de Cataluña (2005SGR01060).</p> <p class="elsevierStyleNotepara">J. Martínez-Llorens was supported by institutional funding from SEPAR, the Catalan Society of Pulmonology (SOCAP), and the Municipal Institute for Medical Research (IMIM, grants for residents, 2002 and 2003).</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:36 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Global Initiative for Chronic Obstructive Lung Disease. Estrategia global para diagnóstico, tratamiento y prevención de la enfermedad pulmonar obstructiva crónica. Reunión de trabajo NHLBI/WHO. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 6 | 4 | 10 |
| 2024 October | 32 | 27 | 59 |
| 2024 September | 34 | 23 | 57 |
| 2024 August | 50 | 46 | 96 |
| 2024 July | 31 | 23 | 54 |
| 2024 June | 32 | 21 | 53 |
| 2024 May | 37 | 26 | 63 |
| 2024 April | 13 | 23 | 36 |
| 2024 March | 19 | 17 | 36 |
| 2024 February | 20 | 19 | 39 |
| 2023 March | 2 | 3 | 5 |
| 2023 February | 20 | 19 | 39 |
| 2023 January | 20 | 30 | 50 |
| 2022 December | 20 | 18 | 38 |
| 2022 November | 22 | 23 | 45 |
| 2022 October | 26 | 30 | 56 |
| 2022 September | 20 | 20 | 40 |
| 2022 August | 19 | 40 | 59 |
| 2022 July | 17 | 70 | 87 |
| 2022 June | 20 | 31 | 51 |
| 2022 May | 13 | 37 | 50 |
| 2022 April | 17 | 26 | 43 |
| 2022 March | 18 | 37 | 55 |
| 2022 February | 19 | 22 | 41 |
| 2022 January | 19 | 34 | 53 |
| 2021 December | 18 | 47 | 65 |
| 2021 November | 19 | 50 | 69 |
| 2021 October | 26 | 45 | 71 |
| 2021 September | 15 | 73 | 88 |
| 2021 August | 15 | 29 | 44 |
| 2021 July | 12 | 29 | 41 |
| 2021 June | 15 | 42 | 57 |
| 2021 May | 15 | 32 | 47 |
| 2021 April | 29 | 66 | 95 |
| 2021 March | 17 | 18 | 35 |
| 2021 February | 26 | 19 | 45 |
| 2021 January | 17 | 19 | 36 |
| 2020 December | 10 | 19 | 29 |
| 2020 November | 14 | 15 | 29 |
| 2020 October | 14 | 13 | 27 |
| 2020 September | 11 | 4 | 15 |
| 2020 August | 26 | 14 | 40 |
| 2020 July | 50 | 16 | 66 |
| 2020 June | 10 | 7 | 17 |
| 2020 May | 19 | 22 | 41 |
| 2020 April | 10 | 17 | 27 |
| 2020 March | 22 | 9 | 31 |
| 2020 February | 20 | 22 | 42 |
| 2020 January | 27 | 13 | 40 |
| 2019 December | 21 | 16 | 37 |
| 2019 November | 17 | 9 | 26 |
| 2019 October | 7 | 11 | 18 |
| 2019 September | 6 | 15 | 21 |
| 2019 August | 14 | 8 | 22 |
| 2019 July | 16 | 21 | 37 |
| 2019 June | 12 | 13 | 25 |
| 2019 May | 17 | 15 | 32 |
| 2019 April | 28 | 18 | 46 |
| 2019 March | 17 | 21 | 38 |
| 2019 February | 13 | 9 | 22 |
| 2019 January | 7 | 4 | 11 |
| 2018 December | 7 | 14 | 21 |
| 2018 November | 20 | 17 | 37 |
| 2018 October | 32 | 17 | 49 |
| 2018 September | 11 | 11 | 22 |
| 2018 May | 2 | 0 | 2 |
| 2018 April | 12 | 8 | 20 |
| 2018 March | 7 | 4 | 11 |
| 2018 February | 5 | 5 | 10 |
| 2018 January | 17 | 11 | 28 |
| 2017 December | 3 | 3 | 6 |
| 2017 November | 4 | 3 | 7 |
| 2017 October | 10 | 10 | 20 |
| 2017 September | 2 | 3 | 5 |
| 2017 August | 9 | 11 | 20 |
| 2017 July | 9 | 7 | 16 |
| 2017 June | 11 | 18 | 29 |
| 2017 May | 8 | 6 | 14 |
| 2017 April | 3 | 3 | 6 |
| 2017 March | 6 | 7 | 13 |
| 2017 February | 5 | 5 | 10 |
| 2017 January | 3 | 6 | 9 |
| 2016 December | 11 | 10 | 21 |
| 2016 November | 7 | 7 | 14 |
| 2016 October | 8 | 7 | 15 |
| 2016 September | 4 | 6 | 10 |
| 2016 August | 6 | 4 | 10 |
| 2016 July | 7 | 6 | 13 |
| 2016 March | 2 | 0 | 2 |
| 2016 February | 1 | 0 | 1 |
| 2015 December | 2 | 0 | 2 |
| 2015 October | 32 | 12 | 44 |
| 2015 September | 38 | 11 | 49 |
| 2015 August | 32 | 11 | 43 |
| 2015 July | 39 | 6 | 45 |
| 2015 June | 27 | 5 | 32 |
| 2015 May | 50 | 10 | 60 |
| 2015 April | 31 | 8 | 39 |
| 2015 March | 40 | 9 | 49 |
| 2015 February | 35 | 3 | 38 |
| 2015 January | 22 | 6 | 28 |
| 2014 December | 37 | 10 | 47 |
| 2014 November | 25 | 6 | 31 |
| 2014 October | 29 | 7 | 36 |
| 2014 September | 29 | 7 | 36 |
| 2014 August | 29 | 7 | 36 |
| 2014 July | 29 | 10 | 39 |
| 2014 June | 30 | 9 | 39 |
| 2014 May | 47 | 9 | 56 |
| 2014 April | 42 | 9 | 51 |
| 2014 March | 49 | 12 | 61 |
| 2014 February | 43 | 9 | 52 |
| 2014 January | 39 | 8 | 47 |
| 2013 December | 39 | 11 | 50 |
| 2013 November | 62 | 7 | 69 |
| 2013 October | 45 | 9 | 54 |
| 2013 September | 39 | 27 | 66 |
| 2013 August | 41 | 5 | 46 |
| 2013 July | 59 | 10 | 69 |
| 2013 June | 37 | 6 | 43 |
| 2013 May | 35 | 6 | 41 |
| 2013 April | 23 | 3 | 26 |
| 2013 March | 11 | 1 | 12 |
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