Department of Orthopedics, The Third Xiangya Hospital, Central South University, Changsha 410013, China.
Department of Orthopedics, The Third Xiangya Hospital, Central South University, Changsha 410013, China
Biosci Rep. 2017 Aug 21;37(4). doi: 10.1042/BSR20170755. Print 2017 Aug 31.
Spinal cord injury (SCI) makes a major contribution to disability and deaths worldwide. Reactive astrogliosis, a typical feature after SCI, which undergoes varying molecular and morphological changes, is ubiquitous but poorly understood. Reactive astrogliosis contributes to glial scar formation that impedes axonal regeneration. Brain-derived neurotrophic factor (BDNF), a well-established neurotrophic factor, exerts neuroprotective and growth-promoting effects on a variety of neuronal populations after injury. In the present study, by using LPS-induced injury model of astroglial cultures, we observed a high expression of interleukin (IL)-6, IL-1β, and BDNF in LPS-stimulated normal human astrocytes (NHAs). BDNF significantly promoted NHA proliferation. Further, online tools were employed to screen the candidate miRNAs which might directly target BDNF to inhibit its expression. Amongst the candidate miRNAs, expression was down-regulated by LPS stimulation in a dose-dependent manner. Through direct targetting, inhibited BDNF expression. Ectopic expression significantly suppressed NHA proliferation, as well as LPS-induced activation of PI3K/Akt pathway. In contrast, inhibition of expression significantly promoted NHA proliferation and LPS-induced activation of PI3K/Akt pathway. Taken together, /BDNF axis regulates LPS-induced NHA proliferation through PI3K/AKT pathway; /BDNF might serve as a promising target in the strategy against reactive astrocyte proliferation after SCI.
脊髓损伤 (SCI) 是全球残疾和死亡的主要原因。反应性星形胶质细胞增生是 SCI 后的一个典型特征，经历了不同的分子和形态变化，普遍存在但了解甚少。反应性星形胶质细胞增生有助于形成胶质瘢痕，阻碍轴突再生。脑源性神经营养因子 (BDNF) 是一种成熟的神经营养因子，在损伤后对多种神经元群体发挥神经保护和促进生长的作用。在本研究中，通过使用 LPS 诱导的星形胶质细胞培养物损伤模型，我们观察到 LPS 刺激的正常人星形胶质细胞 (NHAs) 中白细胞介素 (IL)-6、IL-1β 和 BDNF 的高表达。BDNF 显著促进 NHA 增殖。此外，还使用在线工具筛选可能直接靶向 BDNF 以抑制其表达的候选 miRNA。在候选 miRNA 中，miR-124 表达被 LPS 刺激以剂量依赖性方式下调。通过直接靶向作用，miR-124 抑制 BDNF 表达。外源性 miR-124 表达显著抑制 NHA 增殖以及 LPS 诱导的 PI3K/Akt 通路激活。相反，抑制 miR-124 表达显著促进 NHA 增殖和 LPS 诱导的 PI3K/Akt 通路激活。总之，/BDNF 轴通过 PI3K/AKT 通路调节 LPS 诱导的 NHA 增殖；/BDNF 可能成为 SCI 后反应性星形胶质细胞增殖的有前途的靶点。
