Wang Yongdi, Liao Jinxu, Tang Shao-Jun, Shu Jianhong, Zhang Wenping
College of Life Science, Zhejiang Sci-Tech University, Hangzhou, 310018, China.
Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX, 77555, USA.
J Mol Neurosci. 2017 Jun;62(2):199-208. doi: 10.1007/s12031-017-0931-z. Epub 2017 May 30.
HIV-1 gp120 plays a critical role in the pathogenesis of HIV-associated pain, but the underlying molecular mechanisms are incompletely understood. This study aims to determine the effect and possible mechanism of HIV-1 gp120 on BDNF expression in BV2 cells (a murine-derived microglial cell line). We observed that gp120 (10 ng/ml) activated BV2 cells in cultures and upregulated proBDNF/mBDNF. Furthermore, gp120-treated BV2 also accumulated Wnt3a and β-catenin, suggesting the activation of the Wnt/β-catenin pathway. We demonstrated that activation of the pathway by Wnt3a upregulated BDNF expression. In contrast, inhibition of the Wnt/β-catenin pathway by either DKK1 or IWR-1 attenuated BDNF upregulation induced by gp120 or Wnt3a. These findings collectively suggest that gp120 stimulates BDNF expression in BV2 cells via the Wnt/β-catenin signaling pathway.
HIV-1糖蛋白120(gp120)在HIV相关性疼痛的发病机制中起关键作用,但其潜在的分子机制尚未完全明确。本研究旨在确定HIV-1 gp120对BV2细胞(一种源自小鼠的小胶质细胞系)中脑源性神经营养因子(BDNF)表达的影响及可能机制。我们观察到,gp120(10纳克/毫升)可激活培养中的BV2细胞,并上调前体BDNF/成熟BDNF。此外,经gp120处理的BV2细胞还积累了Wnt3a和β-连环蛋白,提示Wnt/β-连环蛋白信号通路被激活。我们证明,Wnt3a激活该信号通路可上调BDNF表达。相反,Dickkopf-1(DKK1)或IWR-1抑制Wnt/β-连环蛋白信号通路可减弱gp120或Wnt3a诱导的BDNF上调。这些研究结果共同表明,gp120通过Wnt/β-连环蛋白信号通路刺激BV2细胞中BDNF的表达。