Modulating Fibro/Adipogenic Precursors to Prevent Adipogenic Replacement of Muscle

调节纤维/脂肪形成前体以防止肌肉的脂肪形成替代

基本信息

批准号：
10408662
负责人：
Marshall Hogarth
金额：
$ 9.93万
依托单位：
CHILDREN'S RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-21 至 2026-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10408662
关键词：
Adipocytes Adipose tissue Adopted Annexins Apoptosis Batimastat Calcium Cells Chronic Clinical Clinical Research DYSF gene Degenerative Disorder Disease Progression Drug usage Duchenne muscular dystrophy Event Exercise Failure Fiber Goals Homeostasis Immune Impairment In Vitro Inflammation Inflammatory Injury Lead Life Limb-Girdle Muscular Dystrophies Lipids Mediating Mus Muscle Muscle Fibers Muscle Weakness Muscle function Muscular Atrophy Muscular Dystrophies Mutation Myopathy Natural regeneration Nature Onset of illness Pathologic Pathology Pathway interactions Patients Pharmaceutical Preparations Population Preclinical Testing Process Proliferating Research Role Severity of illness Signal Transduction Symptoms Testing Therapeutic Transforming Growth Factor beta Work drug efficacy dysferlinopathies effective therapy extracellular improved in vivo lipid biosynthesis macrophage mouse model muscle degeneration muscle regeneration myogenesis new therapeutic target novel prevent progenitor repaired single-cell RNA sequencing smoothened signaling pathway transcriptome sequencing

项目摘要

ABSTRACT. Successful muscle regeneration requires an elaborate cellular choreography between multiple cell populations to remove and replace damaged fibers. Disruption of this choreography leads to muscle degeneration and fibrotic or adipogenic replacement of myofibers. This phenomenon is particularly prevalent in muscular dystrophies, where progressive muscle loss leads to severe debilitation and early loss of life. Hence, there is growing need to understand the cell populations and their interactions which contribute to myofiber regeneration, but can lead to fibrotic or adipogenic replacement when gone awry. This project aims to understand the mechanism underlying impaired cellular interactions leading to myofiber loss and muscle weakness in limb girdle muscular dystrophy type 2B and test approaches to prevent this impairment. This understanding will help develop novel targeted therapeutic approaches to arrest disease progression in this and other muscular dystrophies that are currently without effective treatment options.

抽象的。成功的肌肉再生需要多个细胞之间精心设计的细胞编排细胞群去除和替换受损的纤维。这种编排的破坏会导致肌肉退化和肌纤维的纤维化或脂肪形成替代。这种现象是在肌营养不良症中尤其普遍，进行性肌肉丧失会导致严重的衰弱和早逝。因此，越来越需要了解细胞群体及其相互作用有助于肌纤维再生，但可能导致出现问题时进行纤维化或脂肪形成替代。该项目旨在了解细胞相互作用受损导致肌纤维损失和肌肉的潜在机制 2B 型肢带型肌营养不良症的无力以及预防这种情况的测试方法损害。这种理解将有助于开发新的靶向治疗方法阻止这种肌营养不良症和其他目前尚无的肌营养不良症的疾病进展有效的治疗方案。