Claudin 14/15 play important roles in early wallerian degeneration after rat sciatic nerve injury

Purpose:Wallerian degeneration(WD)is an antegrade degenerative process distal to peripheral nerve injury.Numerous genes are differentially regulated in response to the process.However,the underlying mechanism is unclear,especially the early response.We aimed at investigating the effects of sciatic nerve injury on WD via CLDN 14/15 interactionsin vivo andin vitro.Methods:Using the methods of molecular biology and bioinformatics analysis,we investigated the molecular mechanism by which claudin 14/15 participate in WD.Our previous study showed that claudins 14 and 15 trigger the early signal flow and pathway in damaged sciatic nerves.Here,we report the effects of the interaction between claudin 14 and claudin 15 on nerve degeneration and regeneration during early WD.Results:It was found that claudin 14/15 were upregulated in the sciatic nerve in WD.Claudin 14/15 promoted Schwann cell proliferation,migration and anti-apoptosisin vitro.PKCα,NT3,NF2,and bFGF were significantly upregulated in transfected Schwann cells.Moreover,the expression levels of theβ-catenin,p-AKT/AKT,p-c-jun/c-jun,and p-ERK/ERK signaling pathways were also significantly altered.Conclusion:Claudin 14/15 affect Schwann cell proliferation,migration,and anti-apoptosis via theβ-catenin,p-AKT/AKT,p-c-jun/c-jun,and p-ERK/ERK pathwaysin vitro andin vivo.The results of this study may help elucidate the molecular mechanisms of the tight junction signaling pathway underlying peripheral nerve degeneration.