The Role of bFGF in the Excessive Activation of Astrocytes Is Related to the Inhibition of TLR4/NFκB Signals.
The Role of bFGF in the Excessive Activation of Astrocytes Is Related to the Inhibition of TLR4/NFκB Signals.
复制标题
bFGF在星形胶质细胞过度激活中的作用与TLR4/NF kappa B信号的抑制有关
DOI：
10.3390/ijms17010037
复制
发表时间：
2015-12-28
影响因子：
5.6
通讯作者：
Zhang H
中科院分区：
文献类型：
--
作者：
Ye L;Yang Y;Zhang X;Cai P;Li R;Chen D;Wei X;Zhang X;Xu H;Xiao J;Li X;Lin L;Zhang H
星形胶质细胞在中枢神经系统（CNS）中的免疫防御、稳态、代谢和突触重塑和功能中具有关键作用;然而，在神经元创伤、感染、缺血、中风和神经退行性疾病之后，具有增加的中间丝的星形胶质细胞的过度活化导致促炎性环境并促进神经元死亡。作为一种重要的神经营养因子，内源性碱性成纤维细胞生长因子（basic fibroblast growth factor，bFGF）的分泌有助于神经元细胞的保护作用，但bFGF在反应性星形胶质细胞增生中的作用机制尚不清楚。在这项研究中，我们证明了外源性bFGF通过减少胶质细胞酸性蛋白（GFAP）和其他标志物（包括神经聚糖和波形蛋白，但不包括巢蛋白）的表达来减弱星形胶质细胞活化，并降低促炎细胞因子（如白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α））的水平，通过调控上游Toll样受体4/核因子κB（TLR 4/NFκB）信号通路。我们的研究表明，bFGF的功能不仅与神经保护和神经营养作用有关，而且还参与抑制神经元损伤后过度的星形胶质细胞增生和胶质瘢痕形成。
Astrocytes have critical roles in immune defense, homeostasis, metabolism, and synaptic remodeling and function in the central nervous system (CNS); however, excessive activation of astrocytes with increased intermediate filaments following neuronal trauma, infection, ischemia, stroke, and neurodegenerative diseases results in a pro-inflammatory environment and promotes neuronal death. As an important neurotrophic factor, the secretion of endogenous basic fibroblast growth factor (bFGF) contributes to the protective effect of neuronal cells, but the mechanism of bFGF in reactive astrogliosis is still unclear. In this study, we demonstrated that exogenous bFGF attenuated astrocyte activation by reducing the expression of glial fibrillary acidic protein (GFAP) and other markers, including neurocan and vimentin, but not nestin and decreased the levels of pro-inflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), via the regulation of the upstream toll-like receptor 4/nuclear factor κB (TLR4/NFκB) signaling pathway. Our study suggests that the function of bFGF is not only related to the neuroprotective and neurotrophic effect but also involved in the inhibition of excessive astrogliosis and glial scarring after neuronal injury.