p75NTR and Sortilin Increase After Facial Nerve Injury
p75NTR and Sortilin Increase After Facial Nerve Injury
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DOI：
10.1097/mlg.0b013e31814b8d9f
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发表时间：
2008-01-01
期刊：
影响因子：
2.6
通讯作者：
Hansen, Marlan R.
中科院分区：
文献类型：
--
作者：
Provenzano, Matthew J.;Xu, Ningyong;Hansen, Marlan R.
目的：在轴突切断后，成功的神经再生所需的雪旺细胞（SC）经历许多细胞变化，包括去分化、增殖、支持轴突生长的分子的表达和凋亡。本研究调查的作用p75（NTR），分拣蛋白，和proneurotrophins在SC的生存面神经（FN）axotomy.Study设计：初步animal study.Methods：使用FN SC，表达p75（NTR）和它的coreceptor分拣蛋白进行了定量免疫荧光在第12天，22日和52后axotomy在体内，并通过Western blot在体外。双侧FN作为对照。用末端脱氧核苷酸转移酶缺口末端标记法（TUNEL）检测SC凋亡。为了验证p75（NTR）在FN SC死亡中的致病作用，用促神经生长因子（NGF）处理培养的FN SC，并通过TUNEL测定细胞凋亡。结果：在所有时间点，与对侧对照相比，在轴突切断远端的FN SC中p75（NTR）和分拣蛋白的表达增加（P < .05）。与对侧和近端相比，远段SC凋亡也显著增加（P <0.05）。结论：FN轴突切断可增加SC中p75（NTR）和sortilin的表达，并与细胞凋亡增加有关。这些发现表明p75（NTR）和分拣蛋白在FN损伤后SC损失中的作用。分拣蛋白是促进损伤后FN愈合的新靶点。
Objectives: After axotomy, Schwann cells (SCs), required for successful nerve regeneration, undergo a number of cellular changes including dedifferentiation, proliferation, expression of molecules that support axon growth, and apoptosis. This study investigated the role of p75(NTR), sortilin, and proneurotrophins in SC survival after facial nerve (FN) axotomy.Study Design: Preliminary animal study.Methods: With use of FN SCs, expression of p75(NTR) and its coreceptor sortilin were quantified by immunofluorescence on days 12, 22, and 52 after axotomy in vivo and by Western blot in vitro. Contralateral FNs served as a control. SC apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). To verify a causative role for p75(NTR) in FN SC death, cultured FN SCs were treated with pro-nerve growth factor (NGF), and apoptosis was determined by TUNEL.Results: Expression of p75(NTR) and sortilin increased in FN SCs distal (P < .05) to the axotomy compared with the contralateral controls for all time points. SC apoptosis also significantly increased in the distal segment compared with the contralateral and proximal portions (P < .05). ProNGF, a p75(NTR) ligand, increased apoptosis and p75(NTR) expression in primary FN SC cultures.Conclusion: FN axotomy increases p75(NTR) and sortilin expression in SCs, which correlates with increased apoptosis. These findings suggest roles for p75(NTR) and sortilin in SC loss after FN injury. Sortilin is a novel target in promoting FN healing after injury.