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Mol Ther. 2015 Jun;23(6):1003-1021. doi: 10.1038/mt.2015.40. Epub 2015 Mar 12.

Action of obestatin in skeletal muscle repair: stem cell expansion, muscle growth, and microenvironment remodeling.

Author information

1
Área de Endocrinología Molecular y Celular, Instituto de Investigación Sanitaria de Santiago (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS), Servicio Gallego de Salud (SERGAS), Santiago de Compostela, Spain; CIBER Fisiopatología de la Obesidad y Nutrición, Spain; Current address: Sprott Centre for Stem Cell Research, Ottawa Health Research Institute, Ottawa, Canada.
2
Área de Endocrinología Molecular y Celular, Instituto de Investigación Sanitaria de Santiago (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS), Servicio Gallego de Salud (SERGAS), Santiago de Compostela, Spain; CIBER Fisiopatología de la Obesidad y Nutrición, Spain.
3
CIBER Fisiopatología de la Obesidad y Nutrición, Spain; Departamento de Fisiología, Universidad de Santiago de Compostela (USC), Santiago de Compostela, Spain.
4
Department of Anatomical, Histological, Forensic & Orthopaedic Sciences, Sapienza University of Rome, Rome, Italy; Interuniversity Institute of Myology, Rome, Italy.
5
Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Canada.
6
Unidad de Inmunología, CHUS, Santiago de Compostela, Spain.
7
Servicio de Cirugía Ortopédica y Traumatología, CHUS, SERGAS, Santiago de Compostela, Spain.
8
Departamento de Ciencias Morfológicas, USC, Santiago de Compostela, Spain.
9
Área de Endocrinología Molecular y Celular, Instituto de Investigación Sanitaria de Santiago (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS), Servicio Gallego de Salud (SERGAS), Santiago de Compostela, Spain; CIBER Fisiopatología de la Obesidad y Nutrición, Spain; Departamento de Medicina, USC, Santiago de Compostela, Spain.
10
Área de Endocrinología Molecular y Celular, Instituto de Investigación Sanitaria de Santiago (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS), Servicio Gallego de Salud (SERGAS), Santiago de Compostela, Spain; CIBER Fisiopatología de la Obesidad y Nutrición, Spain. Electronic address: jesus.perez@usc.es.

Abstract

The development of therapeutic strategies for skeletal muscle diseases, such as physical injuries and myopathies, depends on the knowledge of regulatory signals that control the myogenic process. The obestatin/GPR39 system operates as an autocrine signal in the regulation of skeletal myogenesis. Using a mouse model of skeletal muscle regeneration after injury and several cellular strategies, we explored the potential use of obestatin as a therapeutic agent for the treatment of trauma-induced muscle injuries. Our results evidenced that the overexpression of the preproghrelin, and thus obestatin, and GPR39 in skeletal muscle increased regeneration after muscle injury. More importantly, the intramuscular injection of obestatin significantly enhanced muscle regeneration by simulating satellite stem cell expansion as well as myofiber hypertrophy through a kinase hierarchy. Added to the myogenic action, the obestatin administration resulted in an increased expression of vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor 2 (VEGFR2) and the consequent microvascularization, with no effect on collagen deposition in skeletal muscle. Furthermore, the potential inhibition of myostatin during obestatin treatment might contribute to its myogenic action improving muscle growth and regeneration. Overall, our data demonstrate successful improvement of muscle regeneration, indicating obestatin is a potential therapeutic agent for skeletal muscle injury and would benefit other myopathies related to muscle regeneration.

PMID:
25762009
PMCID:
PMC4817756
DOI:
10.1038/mt.2015.40
[Indexed for MEDLINE]
Free PMC Article

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