Dynamic Changes Of Jab1 And P27kip1 Expression In Injured Rat Sciatic Nerve

Objective This study was carried out to observe Jab1 protein expression change and cellular localization after sciatic nerve crush(SNC), and investigate the relationship between Jab1 and Schwann cells proliferation after SNC, and analyse the function of Jab1 in the sciatic nerve crush and repair progress. We also investigate the interaction and possible mechanisms between Jab1 and p27kip1, and further analyse the clinical significance of its network regulation for the therapy in SNC.Methods Firstly, we succeed to make a sciatic nerve crush model by Sprague Dawley(SD) rats. After sciatic nerves were crushed, we observed the expression change and cellular localization of Jab1 through western blot, immunohistochemistry and double immunofluorescent staining. We also used the co-immunoprecipitation and double immunofluorescent staining techniques to investigate the interaction between Jab1 and p27kip1. Combined with those findings, we further analyse its pathophysiological significance in the Schwann cells proliferation progress after sciatic nerve crush.Results After sciatic nerve crush, the expression of Jab1 and p27kip1 were all changed and they had significant difference(P<0.05). We observed that Jab1 protein began to rise gradually from 12 h, peaked at 5d and then slowly decreased to the normal level at 4 weeks by western blot analyse. The expression change of p27kip1 was opposite to Jab1. The result of Jab1 expression change in immunohistochemistry was in parallel with western blot. The double immunofluorescent staining shown that Jab1 expressed mainly in Schwann cells, but had little co-localization in axon. Besides, the expression change of Jab1 was in parallel with PCNA(proliferating cell nuclear antigen), and Jab1 co-labeled with PCNA in Schwann cells. What’s more, the co-immunoprecipitation analyse indicated that Jab1 interact with p27kip1 in sciatic nerve and double immunofluorescent staining shown that they had co-labeling in Schwann cells.Conclusions The expression of Jab1 and p27kip1 were all changed and they had significant difference(P<0.05), and the expression of p27kip1 was opposite to Jab1 after sciatic nerve crush. Jab1 was mainly localized in the Schwann cells and its expression trend was in parallel with PCNA, and they had co-labeling in Schwann cells. There was an interaction between Jab1 and p27kip1 in sciatic nerve and they had co-labeling in Schwann cells. Combined with the reported interaction between Jab1 and p27kip1 previously, we suggested that Jab1 may promote Schwann cells proliferation by decrease the protein level of p27kip1 and thus involved in the regeneration and repair progress after sciatic nerve injury.