Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Applied Physiology and Kinesiology, College of Health and Human Performance, University of Florida, Gainesville, Florida.
Muscle Nerve. 2019 Oct;60(4):464-473. doi: 10.1002/mus.26641. Epub 2019 Jul 30.
Dysferlin loss-of-function mutations cause muscular dystrophy, accompanied by impaired membrane repair and muscle weakness. Growth promoting strategies including insulin-like growth factor 1 (IGF-1) could provide benefit but may cause strength loss or be ineffective. The objective of this study was to determine whether locally increased IGF-1 promotes functional muscle hypertrophy in dysferlin-null (Dysf ) mice.
Muscle-specific transgenic expression and postnatal viral delivery of Igf1 were used in Dysf and control mice. Increased IGF-1 levels were confirmed by enzyme-linked immunosorbent assay. Testing for skeletal muscle mass and function was performed in male and female mice.
Muscle hypertrophy occurred in response to increased IGF-1 in mice with and without dysferlin. Male mice showed a more robust response compared with females. Increased IGF-1 did not cause loss of force per cross-sectional area in Dysf muscles.
We conclude that increased local IGF-1 promotes functional hypertrophy when dysferlin is absent and reestablishes IGF-1 as a potential therapeutic for dysferlinopathies.
肌营养不良蛋白缺失会导致肌肉营养不良，同时伴有细胞膜修复受损和肌肉无力。生长促进策略，包括胰岛素样生长因子 1（IGF-1），可能会带来益处，但也可能导致力量丧失或无效。本研究的目的是确定局部增加 IGF-1 是否会促进肌营养不良蛋白缺失（Dysf）小鼠的功能性肌肉肥大。
在 Dysf 和对照小鼠中使用肌肉特异性转基因表达和产后病毒传递来增加 Igf1。通过酶联免疫吸附试验确认 IGF-1 水平增加。在雄性和雌性小鼠中进行骨骼肌质量和功能测试。
在有和没有肌营养不良蛋白的小鼠中，增加 IGF-1 会导致肌肉肥大。与雌性相比，雄性小鼠的反应更为强烈。增加 IGF-1 不会导致 Dysf 肌肉的比横截面积力量丧失。
我们的结论是，当肌营养不良蛋白缺失时，局部增加 IGF-1 会促进功能性肥大，并重新确立 IGF-1 作为治疗肌营养不良蛋白病的潜在治疗方法。
