Nerve Growth Factor (NGF) and Its Receptors in Skeletal Muscle Signaling

Abstract

The role of nerve growth factor (NGF) and its receptors in physiology of skeletal muscles has not been extensively studied. However, anti‐NGF transgenic mice expressed skeletal muscle damage resembling myopathy, implying that NGF plays an important role in muscle physiology. Our aim is to evaluate the role of NGF and its receptors in muscle, using C2C12 skeletal muscle cell line and wild type (WT) and homozygote dystrophic dy2J mice muscles.A similar mRNA expression for NGF and it receptors p75NTR and α9β1 integrin was found in C2C12 myoblasts and myotubes, while mRNA for trkA receptor was absent. In addition, C2C12 myoblasts secreted NGF to the media in an amount of 60pg/ml/24h, while NGF was not secreted by C2C12 myotubes. NGF treatment induced ERK1/2 stimulation in C2C12, an effect blocked by VLO5 (a disintegrin with relative selectivity towards α9 integrin). We also characterized mRNA expression of NGF, p75NTR, trkA and α9β1 integrin in WT and dy2J mice. We propose that NGF induced signaling in muscle cells is mediated by coupling of p75NTR and α9β1 integrin, as previously reported for glioma cells. Clarification of the role of NGF in muscle pathophysiology may provide novel understanding on the interaction between neurotrophins receptors and integrins towards possible development of novel drugs for muscle diseases.