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Elucidating Skeletal Muscle Satellite Cell:Microvessel Interactions in Diabetic Muscle

阐明骨骼肌卫星细胞：糖尿病肌肉中微血管的相互作用

基本信息

批准号：
10341143
负责人：
CHRISTOPHER Ronald RATHBONE
金额：
$ 37.5万
依托单位：
UNIVERSITY OF TEXAS SAN ANTONIO
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-03-01 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10341143
关键词：
Address Adult Affect Blood Vessels Blood capillaries Cause of Death Cell physiology Cells Clinical Development Diabetes Mellitus Disease Epidemic Exhibits Functional disorder Glucose Goals Growth Health Health Expenditures Histone Deacetylase Homeostasis Impairment Injury Insulin Insulin Resistance Knowledge Lead Link Lipids Lower Extremity Maintenance Measures Mediating Muscle Muscle Fibers Muscle satellite cell Non-Insulin-Dependent Diabetes Mellitus Operative Surgical Procedures Outcome Patients Proteins Reperfusion Injury Research Research Project Grants Resveratrol Role Signal Transduction Skeletal Muscle Skeletal Muscle Satellite Cells Testing Therapeutic Intervention Tissues Tourniquets United States Vascularization angiogenesis cell type density diabetic exosome glucose disposal improved in vivo insight intervention effect limb amputation muscle regeneration myogenesis novel therapeutics overexpression repaired satellite cell stem cells therapeutic target therapy development tool

项目摘要

PROJECT SUMMARY Skeletal muscle dysfunction contributes significantly to the many sequelae of Type 2 Diabetes (T2D). Although the majority of mechanistic studies directed towards describing diabetic skeletal muscle dysfunction focus on a single cell type, it is more prudent to investigate the mechanistic interaction linking different types of cells. For example, the maintenance of skeletal muscle homeostasis in vivo is a coordinated interaction between the myogenic cells and the vasculature. Satellite cells from myopathic muscle have been shown to have a diminished effect on angiogenesis, so it is reasonable to speculate that satellite cells from diabetic muscle also have a weakened ability to maintain vessel function. An understanding of the coordinated interaction between satellite cells and the vasculature requires an understanding of the mechanisms that regulate satellite cell-mediated effects on angiogenesis. The overall objective of this application is to elucidate the satellite-cell mediated mechanisms that contribute to diabetic skeletal muscle dysfunction. The central hypothesis is that satellite cells derived from diabetic muscle exhibit changes in their exosomes that are manifested as an impaired ability to promote angiogenesis. The completion of the overall objective for this project will be accomplished by pursuing three specific aims: (1) Identify the satellite cell-dependent mechanisms that contribute to impaired angiogenesis in diabetic muscle; (2) Elucidate the role of SIRT1 in mediating satellite cell-dependent mechanisms in diabetic muscle; and, (3) Determine the mechanisms that cause diminished satellite cell-dependent activity in diabetic muscle after ischemia-reperfusion (I/R) injury. The outcome of these three separate, but related, specific aims will be the determination of the mechanisms that control the ability of satellite cells to affect angiogenesis in diabetic muscle, including during repair after injury.

项目摘要骨骼肌功能障碍显著导致2型糖尿病（T2 D）的许多后遗症。虽然大多数针对描述糖尿病骨骼肌功能障碍的机制研究集中在对于单细胞类型，更谨慎的是研究连接不同类型细胞的机制相互作用。为例如，体内骨骼肌稳态的维持是骨骼肌和肌肉之间的协调相互作用。生肌细胞和脉管系统。来自肌病肌肉的卫星细胞已经被证明具有减少的影响血管生成，因此推测来自糖尿病肌肉的卫星细胞也具有维持血管功能的能力减弱。对卫星间协调相互作用的理解细胞和脉管系统需要了解调节卫星细胞介导的对血管生成的影响本申请的总体目标是阐明卫星细胞介导的导致糖尿病骨骼肌功能障碍的机制。核心假设是卫星细胞来源于糖尿病肌肉的外泌体表现出其外泌体的变化，表现为促进血管生成。为实现本项目的总体目标，三个具体目标：（1）确定卫星细胞依赖的机制，有助于受损的血管生成（2）阐明SIRT 1在糖尿病骨骼肌中介导卫星细胞依赖性机制的作用（3）确定糖尿病患者卫星细胞依赖性活动减少的机制。缺血再灌注（I/R）损伤后的肌肉。这三个独立但相关的具体目标的结果将是确定控制卫星细胞影响血管生成能力的机制，糖尿病肌肉，包括损伤后修复期间。