Gelatin Nanostructured Lipid Carriers Incorporating Nerve Growth Factor Inhibit Endoplasmic Reticulum Stress-Induced Apoptosis and Improve Recovery in Spinal Cord Injury
Gelatin Nanostructured Lipid Carriers Incorporating Nerve Growth Factor Inhibit Endoplasmic Reticulum Stress-Induced Apoptosis and Improve Recovery in Spinal Cord Injury
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掺入神经生长因子的明胶纳米结构脂质载体抑制内质网应激诱导的细胞凋亡并改善脊髓损伤的恢复
DOI：
10.1007/s12035-015-9372-2
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发表时间：
2015-08
影响因子：
5.1
通讯作者：
Xiao Jian
中科院分区：
文献类型：
--
作者：
Zhu Si-Pin;Wang Zhou-Guang;Zhao Ying-Zheng;Wu Jiang;Shi Hong-Xue;Ye Li-Bing;Wu Fen-Zan;Cheng Yi;Zhang Hong-Yu;He Songbin;Wei Xiaojie;Fu Xiao-Bing;Li Xiao-Kun;Xu Hua-Zi;Xiao Jian
生长因子疗法的临床转化面临着多重挑战;最重要的挑战是裸蛋白的半衰期短。明胶纳米结构脂质载体（GNLs）以前曾被用来封装碱性成纤维细胞生长因子，以促进偏侧帕金森病大鼠的功能恢复。本研究比较了负载神经生长因子（NGF）的GNLs（NGF-GNLs）与单纯NGF对脊髓损伤（SCI）的强化治疗作用。通过Basso-Beattie-Bresnahan（BBB）运动量表、斜面试验和足迹分析来测试NGF-GNLs和仅NGF的作用。进一步进行Western印迹分析和免疫荧光染色以鉴定ER应激相关蛋白、神经元特异性标记神经元核（NeuN）和生长相关蛋白43（GAP 43）的表达。相关的下游信号Akt/GSK-3β和ERK 1/2也进行了分析，有或没有抑制剂。结果表明，NGF-GNLs对脊髓损伤大鼠的神经保护作用明显优于单独使用NGF。NGF-GNL对ER应激诱导的凋亡反应蛋白CHOP、GRP 78和caspase-12的抑制作用更明显。同时，NGF-GNLs在SCI恢复过程中通过激活下游信号PI 3 K/Akt/GSK-3β和ERK 1/2，抑制ER应激诱导的细胞死亡。
Clinical translation of growth factor therapies faces multiple challenges; the most significant one is the short half-life of the naked protein. Gelatin nanostructured lipid carriers (GNLs) had previously been used to encapsulate the basic fibroblast growth factor to enhance the functional recovery in hemiparkinsonian rats. In this research, we comparatively study the enhanced therapy between nerve growth factor (NGF) loaded GNLs (NGF-GNLs) and NGF only in spinal cord injury (SCI). The effects of NGF-GNLs and NGF only were tested by the Basso-Beattie-Bresnahan (BBB) locomotion scale, inclined plane test, and footprint analysis. Western blot analysis and immunofluorescent staining were further performed to identify the expression of ER stress-related proteins, neuron-specific marker neuronal nuclei (NeuN), and growth-associated protein 43 (GAP43). Correlated downstream signals Akt/GSK-3β and ERK1/2 were also analyzed with or without inhibitors. Results showed that NGF-GNLs, compared to NGF only, enhanced the neuroprotection effect in SCI rats. The ER stress-induced apoptosis response proteins CHOP, GRP78 and caspase-12 inhibited by NGF-GNL treatment were more obvious. Meanwhile, NGF-GNLs in the recovery of SCI are related to the inhibition of ER stress-induced cell death via the activation of downstream signals PI3K/Akt/GSK-3β and ERK1/2.
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影响因子：
14
作者：
Layman, Hans;Spiga, Maria-Grazia;Andreopoulos, Fotios M.
通讯作者：
Andreopoulos, Fotios M.
影响因子：
2.6
作者：
Wuhanqimuge;Itakura A;Matsuki Y;Tanaka M;Arioka M
通讯作者：
Arioka M
影响因子：
9
作者：
通讯作者：
--
影响因子：
5.8
作者：
Ansorena, Eduardo;De Berdt, Pauline;des Rieux, Anne
通讯作者：
des Rieux, Anne
影响因子：
6.2
作者：
Ohri, Sujata Saraswat;Maddie, Melissa A.;Whittemore, Scott R.
通讯作者：
Whittemore, Scott R.