Development of novel strategies to improve skeletal muscle repair and adaptation following eccentric exercise

α7 integrin;Satellite cells;Stem cells;Muscle repair;Downhill running;Aging

Zou, Kai

关键词: α7 integrin;    Satellite cells;    Stem cells;    Muscle repair;    Downhill running;    Aging;   

Others  :  https://www.ideals.illinois.edu/bitstream/handle/2142/49702/Kai_Zou.pdf?sequence=1&isAllowed=y

美国|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

Eccentric contractions, often required for participation in resistance training, as well as daily activities, can injure skeletal muscle. The repair of muscle damage is essential for effective remodeling, tissue maintenance, and initiation of beneficial adaptations post-exercise. We have previously demonstrated that transgenic overexpression of the α7BX2 integrin in skeletal muscle (MCK: α7BX2; α7Tg) enhances muscle repair and the adaptive response following eccentric exercise. Recent studies have provided evidence that mesenchymal stem cells residing in skeletal muscle (mMSCs) contribute to repair following injury by secreting a variety of factors that are important for progenitor cell (satellite cell) activation. Our lab has also previously established that mMSC proliferation and quantity is increased following eccentric exercise in a manner dependent on the presence of the α7BX2 integrin. Preliminary cell culture experiments conducted in our lab suggest that mMSC paracrine factor gene expression is enhanced in the presence of laminin, an important component of the basal lamina that provides the microenvironment for muscle stem cells. Thus, the purpose of this study was to determine the extent to which mMSC and laminin-111 (LM-111) supplementation can enhance muscle repair and/or the adaptive response associated with eccentric exercise. Lipophilic dye-labeled mMSCs (Sca-1+CD45-) isolated from α7Tg muscle post-exercise via FACS were intramuscularly injected into 3 month old WT recipient mice. Controls were injected with equal volume saline. Mice either remained sedentary or were subjected to eccentric exercise training on a treadmill (3x/wk) for two or four weeks following mMSCs transplantation. Gastrocnemius and soleus complexes were collected 24 hours after the last bout of exercise to analyze indices of muscle repair and growth. In a separate study, natural mouse LM-111 was injected intramuscularly into 3 month old WT recipient mice one week prior to exercise. Controls were injected with equal volume saline. Mice either remained sedentary or were subjected to a single bout of eccentric exercise on a treadmill for 30 minutes. Gastronemius and soleus complexes were collected 24 hours post-exercise to analyze indices of muscle repair. In this study, we demonstrate that mMSC supplementation increases satellite cell activation (2-fold compared to all other groups), myonuclear content, myofiber hypertrophy, and hindlimb strength post-exercise. In addition, the presence of supplemental LM-111 markedly increased satellite cell proliferation and content post-exercise. Additional experiments suggest that modification of endogenous mMSC function, including upregulation of hepatocyte growth factor (HGF) gene expression, may be responsible for satellite activation with LM-111.Therefore, these data suggest that mMSC and LM-111 supplementation provide therapeutic strategies to enhance repair following eccentric exercise. Such strategies may not only benefit healthy individuals seeking to accelerate recovery and athletic performance, but also populations that have a limited capacity for skeletal muscle regeneration.