Our recent study demonstrated that knockout of microRNA-301a attenuates migration and phagocytosis in macrophages.Considering that macrophages and Schwann cells synergistically clear the debris of degraded axons and m...Our recent study demonstrated that knockout of microRNA-301a attenuates migration and phagocytosis in macrophages.Considering that macrophages and Schwann cells synergistically clear the debris of degraded axons and myelin during Wallerian degeneration,which is a prerequisite for nerve regeneration,we hypothesized that microRNA-301a regulates Wallerian degeneration and nerve regeneration via impacts on Schwann cell migration and phagocytosis.Herein,we found low expression of microRNA-301a in intact sciatic nerves,with no impact of the microRNA-301a knockout on nerve structure and function.By contrast,we found significant upregulation of microRNA-301a in injured sciatic nerves.We established a sciatic nerve crush model in microRNA-301a knockout mice,which exhibited attenua9ted morphological and functional regeneration following sciatic nerve crush injury.The microRNA-301a knockout also led to significantly inhibited Wallerian degeneration in an in vivo sciatic nerve-transection model and in an in vitro nerve explant block model.Schwann cells with the microRNA-301a knockout showed inhibition of phagocytosis and migration,which was reversible under transfection with microRNA-301a mimics.Rescue experiments involving transfection of microRNA-301a-knockout Schwann cells with microRNA-301a mimics or treatment with the C-X-C motif receptor 4 inhibitor WZ811 indicated the mechanistic involvement of the Yin Yang 1/C-X-C motif receptor 4 pathway in the role of microRNA-301a.Combined with our previous findings in macrophages,we conclude that microRNA-301a plays a key role in peripheral nerve injury and repair by regulating the migratory and phagocytic capabilities of Schwann cells and macrophages via the Yin Yang 1/C-X-C motif receptor 4 pathway.展开更多
基金supported by the National Natural Science Foundation of China,No.82071386(to JG).
文摘Our recent study demonstrated that knockout of microRNA-301a attenuates migration and phagocytosis in macrophages.Considering that macrophages and Schwann cells synergistically clear the debris of degraded axons and myelin during Wallerian degeneration,which is a prerequisite for nerve regeneration,we hypothesized that microRNA-301a regulates Wallerian degeneration and nerve regeneration via impacts on Schwann cell migration and phagocytosis.Herein,we found low expression of microRNA-301a in intact sciatic nerves,with no impact of the microRNA-301a knockout on nerve structure and function.By contrast,we found significant upregulation of microRNA-301a in injured sciatic nerves.We established a sciatic nerve crush model in microRNA-301a knockout mice,which exhibited attenua9ted morphological and functional regeneration following sciatic nerve crush injury.The microRNA-301a knockout also led to significantly inhibited Wallerian degeneration in an in vivo sciatic nerve-transection model and in an in vitro nerve explant block model.Schwann cells with the microRNA-301a knockout showed inhibition of phagocytosis and migration,which was reversible under transfection with microRNA-301a mimics.Rescue experiments involving transfection of microRNA-301a-knockout Schwann cells with microRNA-301a mimics or treatment with the C-X-C motif receptor 4 inhibitor WZ811 indicated the mechanistic involvement of the Yin Yang 1/C-X-C motif receptor 4 pathway in the role of microRNA-301a.Combined with our previous findings in macrophages,we conclude that microRNA-301a plays a key role in peripheral nerve injury and repair by regulating the migratory and phagocytic capabilities of Schwann cells and macrophages via the Yin Yang 1/C-X-C motif receptor 4 pathway.
