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坐骨神经损伤后FBP1和p27kip1的表达:对雪旺细胞增殖和分化的影响

FBP1 and p27kip1 expression after sciatic nerve injury: implications for Schwann cells proliferation and differentiation.

作者信息

Yao Li, Cao Jianhua, Sun Huiqing, Guo Aisong, Li Aihong, Ben Zhiyun, Zhang Haiyan, Wang Xinxiu, Ding Zongmei, Yang Xiaojing, Huang Xianting, Ji Yuhong, Zhou Zhengming

机构信息

Department 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.

出版信息

J Cell Biochem. 2014 Jan;115(1):130-40. doi: 10.1002/jcb.24640.

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.

摘要

远上游元件(FUSE)结合蛋白1(FBP1)最初被鉴定为一种与FUSE结合的单链DNA(ssDNA)结合蛋白,它可以调节c-myc mRNA水平,并且已被证明能够调节肿瘤细胞增殖和病毒复制。通常,FBP1可激活p27kip1(p27)的翻译并参与肿瘤生长。然而,FBP1在周围神经系统损伤和修复中的表达及作用仍不清楚。在我们的研究中,我们发现FBP1蛋白水平在正常坐骨神经中相对较高,在第3天显著降低并达到最低水平,然后在4周时恢复到正常水平。在空间上,我们观察到FBP1主要定位于雪旺细胞中,并且FBP1与Ki-67和Oct-6相关联。在体外,我们在TNF-α诱导的雪旺细胞增殖模型中检测到FBP1和p27水平降低,而在cAMP诱导的雪旺细胞分化系统中表达增加。特别地,FBP1特异性siRNA转染的雪旺细胞在cAMP处理后未表现出良好且更长的形态变化,并且与正常细胞相比运动性降低。在cAMP处理和雪旺细胞/神经元共培养3天后,p27被转运到细胞质中形成CDK4/6-p27以参与雪旺细胞分化。总之,我们推测FBP1和p27通过将p27从细胞核转运到细胞质参与坐骨神经挤压伤后雪旺细胞的增殖及随后的分化。

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