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

Autor: Southern WM; Department of Kinesiology, University of Georgia, Athens, GA, 30602, USA.; Regenerative Bioscience Center, University of Georgia, Athens, GA, 30602, USA., Nichenko AS; Department of Kinesiology, University of Georgia, Athens, GA, 30602, USA.; Regenerative Bioscience Center, University of Georgia, Athens, GA, 30602, USA., Tehrani KF; Regenerative Bioscience Center, University of Georgia, Athens, GA, 30602, USA., McGranahan MJ; Department of Kinesiology, University of Georgia, Athens, GA, 30602, USA., Krishnan L; Parker H. Petit Institute for Bioengineering & Bioscience, Georgia Institute of Technology, Atlanta, GA, 30332, USA., Qualls AE; Department of Kinesiology, University of Georgia, Athens, GA, 30602, USA.; Regenerative Bioscience Center, University of Georgia, Athens, GA, 30602, USA., Jenkins NT; Department of Kinesiology, University of Georgia, Athens, GA, 30602, USA., Mortensen LJ; Regenerative Bioscience Center, University of Georgia, Athens, GA, 30602, USA., Yin H; Center for Molecular Medicine, University of Georgia, Athens, GA, 30602, USA.; Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA, 30602, USA., Yin A; Center for Molecular Medicine, University of Georgia, Athens, GA, 30602, USA.; Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA, 30602, USA., Guldberg RE; Knight Campus for Accelerating Scientific Impact, University of Oregon, Eugene, OR, 97403, USA., Greising SM; School of Kinesiology, University of Minnesota, Minneapolis, MN, 55455, USA., Call JA; Department of Kinesiology, University of Georgia, Athens, GA, 30602, USA. call@uga.edu.; Regenerative Bioscience Center, University of Georgia, Athens, GA, 30602, USA. call@uga.edu.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2019 Mar 11; Vol. 9 (1), pp. 4079. Date of Electronic Publication: 2019 Mar 11.
DOI: 10.1038/s41598-019-40606-6
Abstrakt: 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: MEDLINE
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