We have identified the molecular (transcriptional) signatures associated with muscle remodeling in response to rehabilitation in a patient cohort. Subjects with a closed malleolus fracture treated conservatively with 6 weeks of cast immobilization are recruited. Then subjects are enrolled in a 6 weeks structured rehabilitation program focusing on progressive resistance training of the ankle plantar flexor muscles. Phenotypic measurements are performed before (pre-rehab), during (mid-rehab, 3 weeks) and immediately after (post-rehab, 6 weeks) the rehabilitation intervention. The maximal cross-sectional area (muscle size) and peak torque (muscle strength) are quantified using isometric and isokinetic tests in combination with 3D-magnetic resonance imaging. Ankle plantar flexor muscle size and strength measurements are also performed on the uninvolved limb (serves as a control) at 4 months post-immobilization. Measurements are also acquired from the contralateral leg, which serves as an internal control.
Molecular signatures of differential responses to exercise trainings during rehabilitation.
Sex, Time
View SamplesSpinal cord injury (SCI) is one of the most disabling health problems facing adults today. Locomotor training has been shown to induce substantial recovery in muscle size and muscle function in both transected and contusion injury animal models of SCI.
Transcriptional Pathways Associated with Skeletal Muscle Changes after Spinal Cord Injury and Treadmill Locomotor Training.
Time
View SamplesBackground: Skeletal muscle wasting and impaired muscle function in response to mechanical ventilation and immobilization in intensive care unit (ICU) patients are clinically challenging partly due to (i) the poorly understood intricate cellular and molecular networks; and (ii) the unavailability of an animal model mimicking this condition. By employing a unique porcine model mimicking the conditions in the ICU with long-term mechanical ventilation and immobilization, we have analyzed the expression profile of skeletal muscle biopsies taken at three time points during a five-day period.
Gene expression and muscle fiber function in a porcine ICU model.
Disease, Time
View SamplesBackground :To evaluate the impact of the duration of chronic inflammation on gene expression in skeletal muscle biopsies (MBx) from untreated children with juvenile dermatomyositis (JDM) and identify genes and biological processes associated with the disease progression, expression profiling data from 16 girls with active symptoms of JDM greater or equal to 2 months were compared with 3 girls with active symptoms less than 2 months.
Duration of chronic inflammation alters gene expression in muscle from untreated girls with juvenile dermatomyositis.
No sample metadata fields
View SamplesAlthough short-term disuse does not result in measurable muscle atrophy, studies suggest that molecular changes associated with protein degradation may be initiated within days of the onset of a disuse stimulus. We examined the global gene expression patterns in sedentary men (n = 7, mean age S.D = 22.1 3.7 yr) following 48h unloading (UL) via unilateral lower limb suspension and 24h reloading (RL). Biopsy samples of the left vastus lateralis muscle were collected at baseline, 48h UL, and 24h RL. Expression changes were measured by microarray and gene clustering; identification of enriched functions and canonical pathways were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) and Ingenuity Pathway Analysis (IPA). Four genes were validated with qRT-PCR, and protein levels were measured with Western blot. Of the upregulated genes after UL, the most enriched functional group and highest ranked canonical pathway were related to protein ubiquitination. The oxidative stress response pathway was the second highest ranked canonical pathway. Of the downregulated genes, functions related to mitochondrial metabolism were the mostly highly enriched. In general, gene expression patterns following UL persisted following RL. qRT-PCR confirmed increases in mRNA for UPP-related E3 ligase Atrogin1 (but not accompanying increases in protein products) and stress response gene heme oxygenase-1 (HMOX, which showed a trend towards increases in protein products at 48h UL) as well as extracellular matrix (ECM) component COL4.
Forty-eight hours of unloading and 24 h of reloading lead to changes in global gene expression patterns related to ubiquitination and oxidative stress in humans.
Specimen part, Time
View SamplesFollowing spinal cord injury, skeletal muscle loss is rapid. This severe atrophy is attributed to declines in protein synthesis and increases in protein breakdown. However, the signaling mechanisms controlling these changes are not well understood. Nine male patients and one female patient with spinal cord injury (SCI) (Mean SEM = 43.9 6.7 yrs) were recruited for this study. Six patients were quadriplegics and four patients were paraplegics. Inclusion criteria were as follows: patients above the age of 18 yrs, absence of severe brain injury (Glasgow Coma Scale > 13), absence of muscle-crush injury or compartment syndrome, absence of all of the following conditions: hypoxic injury, systemic sepsis, systemic inflammatory or autoimmune disease, and malignancy. Muscle biopsies were obtained from the vastus lateralis muscles of the SCI patients two days and five days post-SCI. Biopsies collected two days post-SCI were included in the current analysis. Expression changes were measured by microarray and gene clustering; identification of enriched functions and canonical pathways were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) and Ingenuity Pathway Analysis (IPA).
Forty-eight hours of unloading and 24 h of reloading lead to changes in global gene expression patterns related to ubiquitination and oxidative stress in humans.
Specimen part
View SamplesTranscriptomic changes induced by DUX4 expression were compared between human and mouse cell lines of muscle lineage.
DUX4 differentially regulates transcriptomes of human rhabdomyosarcoma and mouse C2C12 cells.
Specimen part
View SamplesFew studies have investigated heterogeneity of selection response in replicate lines subjected to equivalent selection. We developed 4 replicate lines of mice based on high levels of voluntary wheel running (high runner or HR lines) while also maintaining 4 non-selected control lines. This led to the unexpected discovery of the HR mini-muscle (HRmini) phenotype, recognized by a 50% reduction in hindlimb muscle mass, which became fixed in 1 of the 4 HR selected lines.
Gene expression profiling of gastrocnemius of "minimuscle" mice.
Sex, Specimen part
View SamplesGraft versus host disease (GVHD) is the most common complication of hematopoietic stem cell transplant (HCT). However, our understanding of the molecular pathways that cause this disease remains incomplete, leading to inadequate treatment strategies. To address this, we measured the gene expression profile of non-human primate (NHP) T cells during acute GVHD. In this study we specifically interrogated the transcriptional signatures of animals treated with FR104 monotherapy and FR104/Sirolimus combination therapy
Combined OX40L and mTOR blockade controls effector T cell activation while preserving T<sub>reg</sub> reconstitution after transplant.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Transcriptome analysis of GVHD reveals aurora kinase A as a targetable pathway for disease prevention.
Specimen part, Subject
View Samples