Variation in expression of small ubiquitin-like modifiers in injured sciatic nerve of mice

Abstract

Small ubiquitin-like modifiers (SUMOs) have been shown to regulate axonal regeneration, signal transduction, neuronal migration, and myelination, by covalently and reversibly attaching to the protein substrates during neuronal cell growth, development, and differentiation. It has not been reported whether SUMOs play a role in peripheral nerve injury and regeneration. To investigate any association between SUMOylation and potential neuroprotective effects during peripheral nerve injury and regeneration, C57/BL mice were randomly divided into sham and experimental groups. The sciatic nerve was exposed only in the sham group. The experimental group underwent neurotomy and epineurial neurorrhaphy. Real-time quantitative polymerase chain reaction and western blot assay results revealed different mRNA and protein expression levels of SUMO1, SUMO2, SUMO3 and UBC9 in sciatic nerve tissue (containing both 5 mm of proximal and distal stumps at the injury site) at various time points after injury. Compared with the sham group, protein levels of SUMO1 and SUMO2/3 increased in both their covalent and free states after sciatic nerve injury in the experimental group, especially in the covalent state. UBC9 protein levels showed similar changes to those of SUMO1 and SUMO2/3 in the covalent states. Immunohistochemical staining demonstrated that SUMO1 and SUMO2/3 immunopositivities were higher in the experimental group than in the sham group. Our results verified that during the repair of sciatic nerve injury, the mRNA and protein expression of SUMO1, SUMO2, SUMO3 and UBC9 in injured nerve tissues changed in varying patterns and there were clear changes in the expression of SUMO-related proteins. These findings reveal that SUMOs possibly play an important role in the repair of peripheral nerve injury. All animal protocols were approved by the Institutional Animal Care and Use Committee of Tianjin Fifth Central Hospital, China (approval No. TJWZXLL2018041) on November 8, 2018.

Keywords

• nerve regeneration; peripheral nerve injury; sciatic nerve; SUMO1; SUMO2/3; UBC9; SUMOylation; epineurial neurorrhaphy; neural regeneration