Deficient muscle regeneration potential in sarcopenic COPD patients: Role of satellite cells

• Published in: Journal of cellular physiology Vol. 236; no. 4; pp. 3083 - 3098
• Main Authors: Sancho‐Muñoz, Antonio, Guitart, Maria, Rodríguez, Diego A., Gea, Joaquim, Martínez‐Llorens, Juana, Barreiro, Esther
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.04.2021
• Subjects: Antibodies; Cells (biology); Chronic obstructive pulmonary disease; COPD; Damage; DNA nucleotidylexotransferase; Immunofluorescence; lower limb muscles; Markers; Morphometry; muscle regeneration markers; Muscle strength; MyoD protein; Myogenin; Myostatin; Nuclei (cytology); Phenotypes; Quadriceps muscle; Regeneration; Sarcopenia; Satellite cells; muscle regeneration markers; myostatin; lower limb muscles; COPD; satellite cells
• ISSN: 0021-9541; 1097-4652; 1097-4652
• DOI: 10.1002/jcp.30073

Sarcopenia is a major comorbidity in chronic obstructive pulmonary (COPD). Whether deficient muscle repair mechanisms and regeneration exist in the vastus lateralis (VL) of sarcopenic COPD remains debatable. In the VL of control subjects and severe COPD patients with/without sarcopenia, satellite cells (SCs) were identified (immunofluorescence, specific antibodies, anti‐Pax‐7, and anti‐Myf‐5): activated (Pax‐7+/Myf‐5+), quiescent/regenerative potential (Pax‐7+/Myf‐5‐), and total SCs, nuclear activation (terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labeling [TUNEL]), and muscle fiber type (morphometry and slow‐ and fast‐twitch, and hybrid fibers), muscle damage (hematoxylin‐eosin staining), muscle regeneration markers (Pax‐7, Myf‐5, myogenin, and MyoD), and myostatin levels were identified. Compared to controls, in VL of sarcopenic COPD patients, myostatin content, activated SCs, hybrid fiber proportions, TUNEL‐positive cells, internal nuclei, and muscle damage significantly increased, while quadriceps muscle strength, numbers of Pax‐7+/Myf‐5‐ and slow‐ and fast‐twitch, and hybrid myofiber areas decreased. In the VL of sarcopenic and nonsarcopenic patients, TUNEL‐positive cells were greater, whereas muscle regeneration marker expression was lower than in controls. In VL of severe COPD patients regardless of the sarcopenia level, the muscle regeneration process is triggered as identified by SC activation and increased internal nuclei. Nonetheless, a lower regenerative potential along with significant alterations in muscle phenotype and damage, and increased myostatin were prominently seen in sarcopenic COPD. In the vastus lateralis (VL) of severe chronic obstructive pulmonary (COPD) patients regardless of the sarcopenia level, the muscle regeneration process is triggered as identified by satellite cell (SC) activation and increased internal nuclei. Nonetheless, a lower regenerative potential along with significant alterations in muscle phenotype and damage and increased myostatin were prominently seen in sarcopenic COPD.