Gene Expression Profiling Of Skeletal Muscle After Spinal Cord Injury

Abstract OBJECTIVES Thoracic endovascular techniques for aneurysm repair offer less invasive alternatives to open strategies. Both approaches, however, are associated with the risk for neurological complications. Despite adjuncts to maintain spinal cord perfusion, ischaemia and paraplegia continue to occur during thoracoabdominal aortic aneurysm (TAAA) repair. Staging of such extensive procedures has been proven to decrease the risk for spinal cord injury. Archived biopsy specimens may offer insight into the molecular signature of the reorganization and expansion of the spinal collateral network during staged endovascular interventions in the setting of TAAA. METHODS Biological replicates of total RNA were isolated from existing paraspinous muscle samples from 22 Yorkshire pigs randomized to 1 of 3 simulated TAAA repair strategies as part of a previous study employing coil embolization of spinal segmental arteries within the thoracic and lumbar spine. Gene expression profiling was performed using the Affymetrix GeneChip Porcine array. RESULTS Microarray analysis identified 649 differentially expressed porcine genes (≥1.3-fold change, P ≤ 0.05) when comparing paralysed and non-paralysed subjects. Of these, 355 were available for further analysis. When mapped to the human genome, 169 Homo sapiens orthologues were identified. Integrated interpretation of gene expression profiles indicated the significant regulation of transcriptional regulators (such as nuclear factor кB), cytokine (including CXCL12) elements contributing to hypoxia signalling in the cardiovascular system (vascular endothelial growth factor and UBE2) and cytoskeletal elements (like dystrophin (DMD) and matrix metallopeptidase (MMP)). CONCLUSIONS This study demonstrates the ability of microarray-based platforms to detect the differential expression of genes in paraspinous muscle during staged TAAA repair. Pathway enrichment analysis detected subcellular actors accompanying the neuroprotective effects of staged endovascular coiling. These observations provide new insight into the potential prognostic and therapeutic value of gene expression profiling in monitoring and modulating the arteriolar remodelling in the collateral network.

Download Full-text

Impact of short- and long-term electrically induced muscle exercise on gene signaling pathways, gene expression, and PGC1a methylation in men with spinal cord injury

Physiological Genomics ◽

10.1152/physiolgenomics.00064.2019 ◽

2020 ◽

Vol 52 (2) ◽

pp. 71-80

Author(s):

Michael A. Petrie ◽

Arpit Sharma ◽

Eric B. Taylor ◽

Manish Suneja ◽

Richard K. Shields

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Spinal Cord ◽

Spinal Cord Injury ◽

Specific Gene ◽

Muscle Exercise ◽

Gene Sets ◽

Cord Injury ◽

Key Pathways

Exercise attenuates the development of chronic noncommunicable diseases (NCDs). Gene signaling pathway analysis offers an opportunity to discover if electrically induced muscle exercise regulates key pathways among people living with spinal cord injury (SCI). We examined short-term and long-term durations of electrically induced skeletal muscle exercise on complex gene signaling pathways, specific gene regulation, and epigenetic tagging of PGC1a, a major transcription factor in skeletal muscle of men with SCI. After short- or long-term electrically induced exercise training, participants underwent biopsies of the trained and untrained muscles. RNA was hybridized to an exon microarray and analyzed by a gene set enrichment analysis. We discovered that long-term exercise training regulated the Reactome gene sets for metabolism (38 gene sets), cell cycle (36 gene sets), disease (27 gene sets), gene expression and transcription (22 gene sets), organelle biogenesis (4 gene sets), cellular response to stimuli (8 gene sets), immune system (8 gene sets), vesicle-mediated transport (4 gene sets), and transport of small molecules (3 gene sets). Specific gene expression included: oxidative catabolism of glucose including PDHB ( P < 0.001), PDHX ( P < 0.001), MPC1 ( P < 0.009), and MPC2 ( P < 0.007); Oxidative phosphorylation genes including SDHA ( P < 0.006), SDHB ( P < 0.001), NDUFB1 ( P < 0.002), NDUFA2 ( P < 0.001); transcription genes including PGC1α ( P < 0.030) and PRKAB2 ( P < 0.011); hypertrophy gene MSTN ( P < 0.001); and the myokine generating FNDC5 gene ( P < 0.008). Long-term electrically induced exercise demethylated the major transcription factor PGC1a. Taken together, these findings support that long-term electrically induced muscle activity regulates key pathways associated with muscle health and systemic metabolism.

Download Full-text

Differential expression of metabolic genes essential for glucose and lipid metabolism in skeletal muscle from spinal cord injured subjects

Journal of Applied Physiology ◽

10.1152/japplphysiol.00686.2010 ◽

2011 ◽

Vol 110 (5) ◽

pp. 1204-1210 ◽

Cited By ~ 14

Author(s):

Yun Chau Long ◽

Emil Kostovski ◽

Hanneke Boon ◽

Nils Hjeltnes ◽

Anna Krook ◽

...

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Spinal Cord ◽

Spinal Cord Injury ◽

Mrna Levels ◽

Metabolic Gene ◽

Metabolic Gene Expression ◽

Cord Injury ◽

The Impact ◽

Spinal Cord Injured

Skeletal muscle plays an important role in the regulation of energy homeostasis; therefore, the ability of skeletal muscle to adapt and alter metabolic gene expression in response to changes in physiological demands is critical for energy balance. Individuals with cervical spinal cord lesions are characterized by tetraplegia, impaired thermoregulation, and altered skeletal muscle morphology. We characterized skeletal muscle metabolic gene expression patterns, as well as protein content, in these individuals to assess the impact of spinal cord injury on critical determinants of skeletal muscle metabolism. Our results demonstrate that mRNA levels and protein expression of skeletal muscle genes essential for glucose storage are reduced, whereas expression of glycolytic genes is reciprocally increased in individuals with spinal cord injury. Furthermore, expression of genes essential for lipid oxidation is coordinately reduced in spinal cord injured subjects, consistent with a marked reduction of mitochondrial proteins. Thus spinal cord injury resulted in a profound and tightly coordinated change in skeletal muscle metabolic gene expression program that is associated with the aberrant metabolic features of the tissue.

Download Full-text