Molecular Signatures of Muscle Rehabilitation

肌肉康复的分子特征

基本信息

批准号：
7934714
负责人：
KRISTA H VANDENBORNE
金额：
$ 13.84万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2011-09-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7934714
关键词：
Activities of Daily Living Acute Address Aerobic Ankle Area Atrophic Bed rest Biopsy Chronic Clinical Contralateral Critical Care Custom Data Data Analyses Data Set Databases Development Diagnostic Diagnostic Procedure Disease Enrollment Exercise Feedback Female Flexor Fracture Functional Magnetic Resonance Imaging Funding Future Generations Genes Genetic Genetic Polymorphism Goals Heel Human Human Genome Imagery Immobilization Immunoblotting Impairment Individual Injury Intervention Isometric Exercise Isotonic Exercise Leg Limb structure Longitudinal Studies Magnetic Resonance Imaging Measurement Measures Medial Mediating Messenger RNA Modeling Molecular Molecular Profiling Monitor Muscle Muscle Contraction Muscle function Muscle rehabilitation Muscular Atrophy Myopathy Operative Surgical Procedures Outcome Pathway interactions Patients Pattern Performance Phenotype Principal Investigator Proteins Recovery Recovery of Function Recruitment Activity Rehabilitation therapy Relative (related person)Repression Research Personnel Reverse Transcriptase Polymerase Chain Reaction SNP genotyping Sampling Secondary to Secure Specificity Speed Stimulus Structure Study Subject Sum Test Result Testing Therapeutic Intervention Time Torque Training Transcript Transforming Growth Factor beta Validation Variant Walking Woman base cohort conditioning database design design disability fitness healthy volunteer improved longitudinal analysis male men motor control muscle strength novel programs quadriplegic myopathy repaired response restoration strength training success synergism visual coding volunteer web-accessible

项目摘要

DESCRIPTION (provided by applicant): Muscle atrophy and weakness secondary to disuse are common clinical phenomena, which can significantly impact activities of daily living and present a major challenge in rehabilitation. Rehabilitation programs designed to maximize strength gains may not be optimal, and the speed and extent of recovery is highly variable between individuals. We will identify the molecular (transcriptional) signatures associated with muscle remodeling in response to rehabilitation in a patient cohort. The key hypothesis of this proposal is that the rate and extent of functional recovery during rehabilitation following limb disuse correlates with the extent of induction of four remodeling signatures eccentric/damage, TGFbeta/MAPK, atrophy and aerobic conditioning) previously identified by this investigative team. 60 patients with a closed malleolus fracture, treated conservatively using a short leg cast for a period of 6 weeks will be recruited. Following cast-immobilization, subjects will be enrolled in a standardized 6-week rehabilitation program (3 sessions/week) focusing on progressive resistance training of the ankle plantar flexor muscles. The phenotypic response (Aim 1) to cast-immobilization and rehabilitation will be assessed in all individuals using isokinetic testing, magnetic resonance imaging and functional assessment tests. Phenotypic measurements will be performed before, during and immediately after the rehabilitation intervention. Ankle plantar flexor muscle size and strength measurements will also be performed on the uninvolved limb (serves as a control) at 6 months post-immobilization. In Aim 2, four longitudinal biopsies will be taken from the medial gastrocnemius of each individual and expression profiled over the entire human genome (U133A/B). The first 30 individuals will be used as the data generation "test set" (years 1-3), and the second 30 individuals as a "validation set" (years 3-5). In Aim 3, we will determine the correlation between the phenotypes defined in Aim 1 (percentage change in size, muscle strength, functional performance), and the "relative induction/repression" of the four remodeling signatures (eccentric/damage, TGFbeta/MAPK, muscle atrophy and aerobic conditioning). The development of effective therapeutic interventions targeting restoration of muscle function necessitates an in-depth understanding of the cellular and molecular mechanisms mediating muscle atrophy and subsequent repair. We anticipate that this study will provide essential feedback for the design and development of effective, individualized, rehabilitation interventions.

描述（由申请人提供）：废用性肌肉萎缩和无力是常见的临床现象，可显着影响日常生活活动，并对康复提出重大挑战。旨在最大限度地增加力量的康复计划可能不是最佳的，而且恢复的速度和程度因人而异。我们将识别与肌肉重塑相关的分子（转录）特征，以响应患者群体的康复。该提议的关键假设是，肢体废用后康复过程中功能恢复的速度和程度与该研究小组先前确定的四种重塑特征（偏心/损伤、TGFbeta/MAPK、萎缩和有氧调节）的诱导程度相关。将招募 60 名闭合性踝骨骨折患者，使用短腿石膏进行为期 6 周的保守治疗。石膏固定后，受试者将参加为期 6 周的标准化康复计划（每周 3 次），重点关注踝关节跖屈肌的渐进式阻力训练。将使用等速测试、磁共振成像和功能评估测试来评估所有个体对石膏固定和康复的表型反应（目标 1）。表型测量将在康复干预之前、期间和之后立即进行。固定后 6 个月，还将对未受影响的肢体（作为对照）进行踝关节跖屈肌大小和力量测量。在目标 2 中，将从每个个体的腓肠肌内侧进行四次纵向活检，并分析整个人类基因组 (U133A/B) 的表达谱。前 30 个个体将用作数据生成“测试集”（第 1-3 年），后 30 个个体将用作“验证集”（第 3-5 年）。在目标 3 中，我们将确定目标 1 中定义的表型（体型、肌肉力量、功能表现的百分比变化）与四种重塑特征（偏心/损伤、TGFbeta/MAPK）的“相对诱导/抑制”之间的相关性。、肌肉萎缩和有氧调节）。针对肌肉功能恢复的有效治疗干预措施的开发需要深入了解介导肌肉萎缩和随后修复的细胞和分子机制。我们预计这项研究将为设计和开发有效的、个性化的康复干预措施提供必要的反馈。