Up-regulation Of HDAC4 Is Associated With Schwann Cell Proliferation After Sciatic Nerve Crush

Objective This study was conducted to observe HDAC4 protein expression changeand cellular localization following sciatic nerve crush(SNC), and investigate the relationship between HDAC4 and Schwann cells proliferationafter SNC, and analysisthe function of HDAC4 in the sciatic nerve crush and repair progress. We also investigate the possible mechanisms underlyingHDAC4, and further analysis the clinical significance of its network regulation for the therapy in SNC.MethodsFirstly, we established a validsciatic nerve crush model usingSprague Dawley(SD) rats. After sciatic nerves were crushed, we detected the expression change and cellular localization of HDAC4 through western blot,immunohistochemistry and double immunofluorescent staining. We also knocked down the expression of HDAC4 in the Schwann cell proliferation model, thusto analyse its pathophysiological significance in the Schwann cell proliferation progress after sciatic nerve crush.Results After sciatic nerve crush, the expression of HDAC4 changedwith statistical significance(P<0.05). We observed that the protein level of HDAC4 started to rise gradually from12 h, peaked at 5dand then gradually decreased to the normal level at 4 weeks by western blotanalysis.Theexpression change ofHDAC4 shown by immunohistochemistry was in parallel with that of western blot. The double immunofluorescent stainingindicated that HDAC4 expressed mainly in Schwanncells, partially in macrophages, but had little co-localization in axons. Besides, the expression changeof HDAC4 was in parallel with Ki-67,and HDAC4co-labeled withKi67 in Schwanncells.In the Schwann cell proliferation model, the expression of HDAC4 increased gradually while the expression of p21 decreased in the process of Schwan cell proliferatrion. Flow cytometry analysis of cell cycle distribution implied that, depletion of HDAC4 using HDAC4-targeting siRNAsresulted in up-regulated expression of p21 and attenuatedSchwann cell proliferation.ConclusionsThe expression of HDAC4 changed with significant difference(P<0.05) after sciatic nerve crush. HDAC4 expressed mainly in the Schwann cells and its expression trend was in parallel with Ki-67. Also, HDAC4 had co-labeling with ki-67 in Schwanncells. HDAC4 might promote Schwann cell proliferation after SNC viarepression of 21.