Modified insulin-like growth factor 1 containing collagen-binding domain for nerve regeneration.
Modified insulin-like growth factor 1 containing collagen-binding domain for nerve regeneration.
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含有胶原蛋白结合域的修饰胰岛素样生长因子 1 用于神经再生
DOI：
10.4103/1673-5374.226400
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发表时间：
2018-03
影响因子：
6.1
通讯作者：
Zan CF
中科院分区：
文献类型：
--
作者：
Li JA;Zhao CF;Li SJ;Zhang J;Li ZH;Zhang Q;Yang XY;Zan CF
胰岛素样生长因子1（IGF-1）是神经修复的潜在营养素。然而，由于其有限的半衰期、快速清除和有限的靶特异性，其作为治疗是不切实际的。为了实现靶向和持久的治疗，我们研究了通过将胶原结合结构域融合到IGF-1来添加结合结构。在确认其对胶原的亲和力后，通过使用3-（4，5-二甲基-2-噻唑基）-2，5-二苯基-2-H-溴化四唑鎓测定法测量转染到PC 12和Schwann细胞后的细胞增殖来检查该构建体的生物活性。免疫荧光染色检测神经丝和微管相关蛋白2的表达，真实的时间-聚合酶链反应检测IGF-1受体和神经生长因子mRNA的表达。我们的研究结果表明，与IGF-1相比，重组蛋白的胶原结合活性显着增加。重组蛋白能促进PC 12细胞和雪旺细胞的增殖，并能增加神经丝蛋白和微管相关蛋白2的表达。重要的是，重组蛋白还刺激IGF-1受体和神经生长因子mRNA持续表达数天。这些结果表明，重组蛋白达到了靶向和长效治疗的目的，因此可以成为临床上使用的促进神经再生的因子，并具有长期的治疗效果。图形摘要[INLINE：1]
Insulin-like growth factor 1 (IGF-1) is a potential nutrient for nerve repair. However, it is impractical as a therapy because of its limited half-life, rapid clearance, and limited target specificity. To achieve targeted and long-lasting treatment, we investigated the addition of a binding structure by fusing a collagen-binding domain to IGF-1. After confirming its affinity for collagen, the biological activity of this construct was examined by measuring cell proliferation after transfection into PC12 and Schwann cells using a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. Immunofluorescence staining was conducted to detect neurofilament and microtubule-associated protein 2 expression, while real time-polymerase chain reaction was utilized to determine IGF-1 receptor and nerve growth factor mRNA expression. Our results demonstrate a significant increase in collagen-binding activity of the recombinant protein compared with IGF-1. Moreover, the recombinant protein promoted proliferation of PC12 and Schwann cells, and increased the expression of neurofilament and microtubule-associated protein 2. Importantly, the recombinant protein also stimulated sustained expression of IGF-1 receptor and nerve growth factor mRNA for days. These results show that the recombinant protein achieved the goal of targeting and long-lasting treatment, and thus could become a clinically used factor for promoting nerve regeneration with a prolonged therapeutic effect. Graphical Abstract [INLINE:1]
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影响因子：
6.1
作者：
Sacchetti M;Lambiase A
通讯作者：
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影响因子：
4.3
作者：
Nieto-Estévez V;Defterali Ç;Vicario-Abejón C
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影响因子：
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通讯作者：
Itano, T
影响因子：
4.1
作者：
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