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FBP1 and p27kip1 expression after sciatic nerve injury: implications for Schwann cells proliferation and
Li Yao1, Jianhua Cao, Huiqing Sun
1Department of Orthopaedics, Affiliated Jiangyin Hospital of Nantong University, Nantong, Jiangsu 226001, People's Republic of China; Department of Immunology, Medical College, Nantong University, Nantong, Jiangsu 226001, People's Republic of China.
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.
Insights
Far Upstream Element (FUSE) Binding Protein 1 (FBP1) levels decrease after sciatic nerve injury but are crucial for Schwann cell repair and differentiation. FBP1 facilitates p27kip1 (p27) transport, aiding nerve regeneration.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Far Upstream Element (FUSE) Binding Protein 1 (FBP1) is known to regulate c-myc mRNA and tumor cell proliferation.
- Its role in peripheral nervous system repair remains unexplored.
Purpose of the Study:
- To investigate the expression and function of FBP1 in sciatic nerve injury and repair.
- To elucidate the involvement of FBP1 and p27kip1 (p27) in Schwann cell proliferation and differentiation.
Main Methods:
- Western blotting and immunohistochemistry to assess FBP1 and p27 levels in normal and injured sciatic nerves.
- In vitro studies using Schwann cell models of proliferation (TNF-α) and differentiation (cAMP).
- siRNA-mediated knockdown of FBP1 in Schwann cells.
Main Results:
- FBP1 levels decreased significantly post-sciatic nerve crush, correlating with Schwann cell proliferation markers.
- FBP1 and p27 were downregulated in proliferating Schwann cells and upregulated during differentiation.
- FBP1 knockdown impaired Schwann cell differentiation and motility.
- p27 was translocated to the cytoplasm to form CDK4/6-p27 complexes during differentiation.
Conclusions:
- FBP1 and p27 play critical roles in Schwann cell proliferation and differentiation following sciatic nerve injury.
- FBP1 facilitates p27 nuclear-to-cytoplasmic transport, essential for Schwann cell differentiation and nerve repair.
