Angiotensin-(1-7) improves skeletal muscle regeneration


Submitted: 30 October 2023
Accepted: 21 November 2023
Published: 15 December 2023
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Authors

  • Mayalen Valero-Breton Laboratory of Muscle Pathology, Fragility and Aging, Faculty of Life Sciences, Universidad Andres Bello, Santiago, Chile; Millennium Institute on Immunology and Immunotherapy, Faculty of Life Sciences. Universidad Andres Bello, Santiago, Chile. https://orcid.org/0000-0001-6552-2262
  • Franco Tacchi Laboratory of Muscle Pathology, Fragility and Aging, Faculty of Life Sciences, Universidad Andres Bello, Santiago, Chile; Millennium Institute on Immunology and Immunotherapy, Faculty of Life Sciences. Universidad Andres Bello, Santiago, Chile.
  • Johanna Abrigo Laboratory of Muscle Pathology, Fragility and Aging, Faculty of Life Sciences, Universidad Andres Bello, Santiago, Chile; Millennium Institute on Immunology and Immunotherapy, Faculty of Life Sciences. Universidad Andres Bello, Santiago, Chile.
  • Felipe Simon Millennium Institute on Immunology and Immunotherapy, Faculty of Life Sciences, Universidad Andres Bello, Santiago, Chile; Laboratory of Integrative Physiopathology, Department of Biological Sciences, Faculty of Life Sciences, Universidad Andres Bello, Santiago, Chile; Millennium Nucleus of Ion Channel-Associated Diseases (MiNICAD), University of Chile, Santiago, Chile.
  • Daniel Cabrera Department of Gastroenterology, Faculty of Medicine, Pontifical Catholic University of Chile, Santiago, Chile; Faculty of Medical Sciences, Universidad Bernardo O Higgins, Santiago, Chile.
  • Claudio Cabello-Verrugio Laboratory of Muscle Pathology, Fragility and Aging, Faculty of Life Sciences, Universidad Andres Bello, Santiago, Chile; Millennium Institute on Immunology and Immunotherapy, Faculty of Life Sciences. Universidad Andres Bello, Santiago, Chile. https://orcid.org/0000-0001-7273-2102

Skeletal muscle possesses regenerative potential via satellite cells, compromised in muscular dystrophies leading to fibrosis and fat infiltration. Angiotensin II (Ang-II) is commonly associated with pathological states. In contrast, Angiotensin (1-7) [Ang-(1-7)] counters Ang-II, acting via the Mas receptor. While Ang-II affects skeletal muscle regeneration, the influence of Ang-(1-7) remains to be elucidated. Therefore, this study aims to investigate the role of Ang-(1-7) in skeletal muscle regeneration. C2C12 cells were differentiated in the absence or presence of 10 nM of Ang-(1-7). The diameter of myotubes and protein levels of myogenin and myosin heavy chain (MHC) were determined. C57BL/6 WT male mice 16-18 weeks old) were randomly assigned to injury-vehicle, injury-Ang-(1-7), and control groups. Ang-(1-7) was administered via osmotic pumps, and muscle injury was induced by injecting barium chloride to assess muscle regeneration through histological analyses. Moreover, embryonic myosin (eMHC) and myogenin protein levels were evaluated. C2C12 myotubes incubated with Ang-(1-7) showed larger diameters than the untreated group and increased myogenin and MHC protein levels during differentiation. Ang-(1-7) administration enhances regeneration by promoting a larger diameter of new muscle fibers. Furthermore, higher numbers of eMHC (+) fibers were observed in the injured-Ang-(1-7), which also had a larger diameter. Moreover, eMHC and myogenin protein levels were elevated, supporting enhanced regeneration due to Ang-(1-7) administration. Ang-(1-7) effectively promotes differentiation in vitroand improves muscle regeneration in the context of injuries, with potential implications for treating muscle-related disorders.


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