PGC-1α overexpression partially rescues impaired oxidative and contractile pathophysiology following volumetric muscle loss injury

Autor: Laxminarayanan Krishnan, Robert E. Guldberg, Amelia Yin, Anita E. Qualls, Nathan T. Jenkins, William M. Southern, Anna S. Nichenko, Jarrod A. Call, Melissa J. McGranahan, Sarah M. Greising, Hang Yin, Luke J. Mortensen, Kayvan Forouhesh Tehrani
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Male
0301 basic medicine
medicine.medical_specialty
medicine.medical_treatment
Muscle Fibers
Skeletal
lcsh:Medicine
Oxidative phosphorylation
Regenerative Medicine
Regenerative medicine
Article
Mice
03 medical and health sciences
0302 clinical medicine
Muscular Diseases
Internal medicine
medicine
Animals
Humans
Regeneration
Ablative surgery
Muscle Strength
Muscle
Skeletal
Orthopaedic trauma
lcsh:Science
030304 developmental biology
0303 health sciences
Multidisciplinary
Rehabilitation
Muscle loss
business.industry
lcsh:R
Skeletal muscle
Soft tissue
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Pathophysiology
Mitochondria
Disease Models
Animal
Oxidative Stress
030104 developmental biology
medicine.anatomical_structure
Endocrinology
lcsh:Q
business
030217 neurology & neurosurgery
Muscle Contraction
Zdroj: Scientific Reports, Vol 9, Iss 1, Pp 1-17 (2019)
Scientific Reports
ISSN: 2045-2322
DOI: 10.1038/s41598-019-40606-6
Popis: Volumetric muscle loss (VML) injury is characterized by a non-recoverable loss of muscle fibers due to ablative surgery or severe orthopaedic trauma, that results in chronic functional impairments of the soft tissue. Currently, the effects of VML on the oxidative capacity and adaptability of the remaining injured muscle are unclear. A better understanding of this pathophysiology could significantly shape how VML-injured patients and clinicians approach regenerative medicine and rehabilitation following injury. Herein, the data indicated that VML-injured muscle has diminished mitochondrial content and function (i.e., oxidative capacity), loss of mitochondrial network organization, and attenuated oxidative adaptations to exercise. However, forced PGC-1α over-expression rescued the deficits in oxidative capacity and muscle strength. This implicates physiological activation of PGC1-α as a limiting factor in VML-injured muscle’s adaptive capacity to exercise and provides a mechanistic target for regenerative rehabilitation approaches to address the skeletal muscle dysfunction.
Databáze: OpenAIRE
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