The Research And Application Of New Modified RNA Oligos In The Muscle Atrophy Disease

The discovery of new growth factors involved in the regulation of muscle development provides a better understanding of the molecular mechanisms involved in the functions of skeletal muscles. One of the factors is FOXO1,which could markedly up-regulated in skeletal muscle in energy-deprived states such as fasting and severe diabetes. In addition, FOXO1 has been shown to stimulate myotube fusion of primary mouse myoblasts and regulate various cellular functions, including the cell cycle, and apoptosis.Another recently identified growth factor that has been characterized as an important and potent negative regulator related to skeletal muscle growth and inhibitor of myoblast proliferation is myostatin, also called growth and differentiation factor 8. Till now, no direct experiment data was shown to study the relationship between the two genes.Antisense oligonucleotides (AS-ONs ) technology are recent approach in allergy treatment supposed to become a reality in the future. To gain insight into the roles of the new modified RNA oligos role of inhibiting the expression of foxo1 in vitro and in vivo, we transfected these RNA oligos into differentiation C2C12 cells or injected into normal and disease model mice. Our results demonstrated that these new modified RNA oligos could decrease the expression of FOXO1 in mice. Most interestingly, these mice showed increased skeletal muscle mass, and the expression of myostatin was decreased,and the MyoD increased. These results indicated that FOXO1 is involved in the regulation of skeletal muscle mass, especially in the expression of myostatin and MyoD. On the other hand, we showed for the first time when the expression of helix transcription factor FOXO1 was inhibited, the expression of myostatin was reduced both at mRNA and protein level and the expression of MyoD was increased in cells and mice.In summary ,in our study we synthesized new modified RNA oilgos and inhibited FOXO1 expression at mRNA level in cells and mice. In FOXO1 inhibited models, the expression of myostatin and myoD changed, which may explain why muscle mass weighed more compared to control. Further analysis of the molecular mechanism of FOXO1 action in the skeletal muscle is important for finding treatment targets of human muscle- wasting- related disease.