CaMKII-smad1 promotes axonal regeneration of peripheral nerves / 中国组织工程研究

ABSTRACT

BACKGROUND: Axons do not regenerate after central nervous system injury in mammals. It is mainly caused by the inhibitory microenvironment at the site of damage and the weakened self-regeneration ability. Studies have found that peripheral nervous system has certain regeneration ability after injury, so we explore the methods of central nervous system repair by studying the genes promoting peripheral nervous system regeneration. As one of the important protein kinase families of neurons, CaMKII up-regulation can improve the ability of neuron regeneration. Similarly, acute depletion of the Smad1 protein in adult mice also prevented axon regeneration in vivo. These genes can directly or indirectly regulate neuronal axon regeneration, but exactly how they regulate neuronal regeneration is still unclear. OBJECTIVE: To study the effects of CaMKII-Smad1 signaling pathway on axon regeneration of dorsal root ganglion neurons by intraperitoneal injection of CaMKII inhibitor and activator, and explored the mechanism of CaMKII and Smad1 in regulating axon regeneration of dorsal root ganglion neurons. METHODS: Totally 40 ICR mice were randomly divided into four groups: KN93 control group, KN93 experimental group, CdCl2 control group and CdCl2 experimental group. Dorsal root ganglion tissue was taken for in vitro culture after 7 days of continuous administration of CaMKII inhibitor KN93 and activator CdCl2. The length of axonal regeneration of dorsal root ganglion neurons was statistically analyzed after 3 days. Protein expression of p-Smad1 in dorsal root ganglion neurons was detected using western blot assay. RESULTS AND CONCLUSION: (1) Compared with the KN93 control group, axonal regeneration of dorsal root ganglion neurons was inhibited, and the p-Smad1 protein expression was decreased in the KN93 experimental group, showing significant differences. (2) Compared with the CdCl2 control group, axonal regeneration of dorsal root ganglion neurons was promoted, and p-Smad1 protein expression was increased in the CdCl2 experimental group, showing significant differences. (3) The results showed that the CaMKII-Smad1 signaling pathway had a regulatory effect on axonal regeneration of dorsal root ganglion neurons.