Bexarotene To Reduce Skeletal Muscle Atrophy After Spinal Cord Injury Research On The Role And Mechanism

Spinal cord injury(SCI)is a common central nervous system in jury disease with high mortality and disability rate,many complications and poor prognosis,among which skeletal muscle atrophy is one of the most common complications,which seriously affects the physical and mental health of patients.in recent years,the rapid development of stem cell research provide new way for the treatment of skeletal muscle atrophy.Bexarotene(Bex)activates the retinoid X receptors(RXR)and regulates the selective signaling of AKT/PK B subtypes to promote the proliferation,differentiation,and fusion of myocytes to form myoducts.In addition,our previous experimental results showed that Bex may affect the proliferation and differentiation of C2C12 cells by enhancing the expression of Insulin-like growth factor-2(IGF-2),but the mechanism of Bex’s effect on reducing skeletal muscle atrophy after spinal cord injury is still unclear.Therefore this paper aims to study Bex in into the role of muscle differentiation mechanism,and then applied to reduce after spinal cord injury of skeletal muscle atrophy in mice.First of all,the effect of Bex regulation of IGF2 on the differentiation of C2C12 cells was studied,in this study,we interfered with the expression of IGF2 gene in C2C12 cells,the expression levels of myogenic differentiation antigen(Myo D)and myogenin(Myo G)were significantly down-regulated after interference with IGF2 gene,the addition of Bex can significantly weaken the inhibitory effect of IGF2 interference,these results indicated that Bex affected the proliferation and differentiation of C2C12 cells by regulating IGF2.At the same time,we detected key proteins in the PI3K/AKT pathway,and found that the expression of p-AKT protein was down-regulated after IGF2 interference,while the addition of Bex could activate AKT phosphorylation.These results suggest that Bex may activate the PI3K/AKT pathway by regulating IGF2 to affect the proliferation and differentiation of C2C12 cells.Secondly,for further research on Bex of C2C12 cells differentiation through PI3K/AKT pathway.By adding the PI3K/AKT pathway inhibitor into C2C12 cells LY294002,the results show that Bex can promote AKT phosphorylation of activating PI3K/AKT pathway.In addition,Bex could attenuate the inhibitory effect of LY294002 on myogenic differentia tion antigen(Myo D)and myogenin(Myo G),and the effect of Bex became more and more obvious with the passing of time,Bex can significantly change the shape of muscle tubes into thicker and longer,and the number of muscle tubes increases significantly,and the fusion rate of muscle tubes increases.It can be concluded that Bex can promote the differentiation of C2C12 cells by activating PI3K/AKT signaling pathway.Finally,in order to further study Bex in spinal cord injury in mice skeletal muscle to resto re the role of mechanism.By building a model of spinal cord injury in mice,mice Bex was given the more the recovery of lower limb muscle,skeletal muscle wet weight ratio increased,inflammatory infiltration situation improved,increased muscle cross-sectional area,AKT phosphorylation is activated,into the expression of quantity increase muscle differentiation factors.These results indicate that Bex can promote the expression of muscle satellite cells,and then promote the regeneration of skeletal muscle.In summary,Bex can promote the proliferation and differentiation of C2C12 cells by enhancing the expression of IGF2,thus activating PI3K/AKT pathway,and can also activate the proliferation and differentiation of myosatelite cells in mice with spinal cord injury,thus reducing the atrophy of skeletal muscle.This helps us to understand the molecular mechanism of Bex in regulating skeletal muscle regeneration,and provides new ideas and theoretical basis for the treatment of skeletal muscle atrophy after spinal cord injury.