FBP1 and p27kip1 Expression After Sciatic Nerve Injury: Implications for Schwann Cells Proliferation and Differentiation

Abstract

Far Upstream Element (FUSE) Binding Protein 1 (FBP1), first identified as a single-stranded DNA (ssDNA) binding protein that binds to the FUSE, could modulate c-myc mRNA levels and also has been shown to regulate tumor cell proliferation and replication of virus. Typically, FBP1 could active the translation of p27kip1 (p27) and participate in tumor growth. However, the expression and roles of FBP1 in peripheral system lesions and repair are still unknown. In our study, we found that FBP1 protein levels was relatively higher in the normal sciatic nerves, significantly decreased and reached a minimal level at Day 3, and then returned to the normal level at 4 weeks. Spatially, we observed that FBP1 had a major colocation in Schwann cells and FBP1 was connected with Ki-67 and Oct-6. In vitro, we detected the decreased level of FBP1 and p27 in the TNF-α-induced Schwann cells proliferation model, while increased expression in cAMP-induced Schwann cells differentiation system. Specially, FBP1-specific siRNA-transfected SCs did not show fine and longer morphological change after cAMP treatment and had a decreased motility compared with normal. At 3 days after cAMP treatment and SC/neuron co-cultures, p27 was transported to cytoplasm to form CDK4/6-p27 to participate in SCs differentiation. In conclusion, we speculated that FBP1 and p27 were involved in SCs proliferation and the following differentiation in the sciatic nerve after crush by transporting p27 from nucleus to cytoplasm.

Ginsenoside Re Promotes Nerve Regeneration by Facilitating the Proliferation, Differentiation and Migration of Schwann Cells via the ERK- and JNK-Dependent Pathway in Rat Model of Sciatic Nerve Crush Injury

“…Another ginsenoside Rg1 promotes peripheral nerve regeneration in rat model of nerve crush injury (Ma et al 2010). It is well known that S100 (Schwann cell marker), NF200 (neuronal marker), GAP-43 (axonal regeneration marker), Oct6 (promyelinating SC marker), and PCNA (Proliferating cell nuclear antigen) are frequently used as neural regenerative index in the process of SNC (Wu et al 2013;Yao et al 2014). In the present study, we detected these markers in the SNC rat a Western blot analysis of Oct-6 in SNC following Re treatment showed a significant upregulation compared with control groups.…”

“…After incubation for 24 h, cells on the upper chamber were fixed with 4 % paraformaldehyde and stained with toluidine blue before being counted under an inverted microscope. In all experiments, data were collected from triplicate chambers (Yao et al 2014).…”

“…The procedures were in accordance with that described before (Yao et al 2014). Both sciatic nerves were removed from 3-day-old Sprague-Dawley rat pups, shredded using fine forceps, and dissociated by incubating at 37°C for 30 min, with occasional mixing, in 10 ml of phosphatebuffered saline (Sigma) containing 0.1 % collagenase A and 0.25 % trypsin (Sigma).…”

“…Following SNC, Schwann cells undergo the process of dedifferentiation, proliferation, and differentiation, which play a predominant supportive role in the neural recovery (Yao et al 2014). Re has diverse effects.…”

Dixdc1 targets CyclinD1 and p21 via PI3K pathway activation to promote Schwann cell proliferation after sciatic nerve crush

“…2B). To further investigate Dixdc1 functions in the proliferation of SCs, we stimulated SCs with TNF-a to construct a kind of Schwann cell proliferation model in vitro as previously described [20]. Since there had been reports about that CyclinD1 and p21 were downstream targets of DIXDC1 [12], we performed western blot analysis to detect the protein levels of Dixdc1, PCNA, CyclinD1, and p21 during the process of Schwann cell proliferation in our study.…”