Transcriptional Pathways Associated with Skeletal Muscle Changes after Spinal Cord Injury and Treadmill Locomotor Training

[摘要] The genetic and molecular events associated with changes in muscle mass andfunction after SCI and after the implementation of candidate therapeuticapproaches are still not completely known. The overall objective of this study wasto identify key molecular pathways activated with muscle remodeling after SCIand locomotor training. We implemented treadmill training in a well-characterizedrat model of moderate SCI and performed genome wide expression profiling onsoleus muscles at multiple time points: 3, 8, and 14 days after SCI. We found that theactivity of the protein ubiquitination and mitochondrial function related pathwayswas altered with SCI and corrected with treadmill training. The BMP pathway wasdifferentially activated with early treadmill training as shown by IngenuityPathway Analysis. The expression of several muscle mass regulators wasmodulated by treadmill training, includingFst,Jun,Bmpr2,Actr2b, andSmad3. Inaddition, key players in fatty acids metabolism (LplandFabp3) responded toboth SCI induced inactivity and reloading with training. The decrease inSmad3andFstearly after the initiation of treadmill training was confirmed by RT-PCR. Our data suggest that TGFβ/Smad3 signaling may be mainly involved in the decrease in muscle mass observed with SCI, while the BMP pathway was activated with treadmill training.

[学科分类] 基础医学