IL-6 Improves The Proliferation And Differentiation Of Satellite Cells In Long-term Skeletal Muscle Atrophy Via The JAK/STAT3

Background:Muscle atrophy is a very common clinical problem and a variety of diseases can cause skeletal muscle atrophy.Skeletal muscle atrophy result from peripheral nerve damage is a very common clinical disease.But even after the repair of peripheral nerves in clinical treatment,the patient's atrophic skeletal muscle is still difficult to function well and some of the skeletal muscle will continue to shr ink.Satellite cells(SCs)are essential stem cells for muscle regeneration in long-term muscle atrophy,which is associated with a variety of inflammatory cells and inflammatory cytokines.Both in acute and chronic skeletal muscle injury,muscle satellite cells will be activated,so as to repair the damaged muscles.However,in the ongoing process of chronic skeletal muscle injury,the muscle satellite cells in injured skeletal muscle is difficult to continue to proliferate to repair the injury.And many inflammatory factors or inflammatory cells are associated with the proliferation and differentiation of musele satellite cells.Among them,interleukin-6(IL-6),as a classic inflammatory factor,plays a role in promoting tissue regeneration in many tissues.And macrophages with cell phagocytosis,cellular immunity and other functions,also plays a vital role in tissue regeneration.This study was to investigate the effects of IL-6 and macrophages on muscle regeneration in atrophic muscle during long-term skeletal muscle atrophy.Methods:? cell level:skeletal muscle satellite cells from the newborn rat skeletal muscle were separated and purified.Macrophages are extracted from the rat abdominal cavity.Cell experiments were performed according to the differentculture conditions of musecle satellite cells:1.In the control group,satellite cells were cultured in high glucose DMEM(dulbecco's modif ied eagle medium,DMEM)medium.2.In IL-6 group,IL-6 was added to satellite cell culture medium.3.In AG490 group,IL-6 and AG490 were added into the medium as AG490 was an important blocker for JAK/STAT3 channel.4.In MACR group,satellite cells and macrophages were co-cultured.? animal level:In order to further understand the role of IL-6 and macrophages in vivo,and establ ish denervated skeletal muscle atrophy model,the sciatic nerve of SD rats was cut.And then DMEM,IL-6,AG490 and macrophages were intramuscularly injected into atrophic gastrocnemius 8 weeks later.The rats were groups as follow:control group(DMED);IL-6 group(IL-6);AG490(IL-6 and AG490);MACR group(macrophage).In both cell and animal experiments,markers of muscle satellite tissue specificity were used to select indicators of observation,including Desmin,Myod,Pax7 and Myosin.Result:? On cell level,compared with the control group,IL-6 significantly increased the expression of Desmin,Myod,Pax7 and Myosin in satellite cells.However,in the AG490 group,this effect of promoting the proliferation and differentiation of musecesate llite cells was significantly inhibited by AG490.And the expression of satellite cells is still higher than that of the control group at the mRNA I eve I or at the prote in Ieve I.In addition,when the satellite cells and macrophages were co-cultured,the satellite cells showed a low expression of myogenic indicators.? On the animal level:the effects of IL-6 and AG490 are similar to those in cell experiments,IL-6 promotes the proliferation and differentiation of satellite cells in atrophic muscle,while AG490 inhibits this effect.However,unlike the results of cell experiments,after the macrophages were intramuscularly injected into atrophic muscles,Desmin,Myod,Pax7 and Myosin both showed a significant increase in atrophic muscle.Conclusion:IL-6 can promote the regeneration of atrophic muscles and affects them primarily through through the JAK/STAT3 pathway in muscle dystrophy of prolonged denervation.While macrophages are likely to promote the regeneration of atrophic muscles through an indirect way.