NF-κB signaling is key in the wound healing processes of silk fibroin
NF-κB signaling is key in the wound healing processes of silk fibroin
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DOI：
10.1016/j.actbio.2017.12.006
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发表时间：
2018-02-01
影响因子：
9.7
通讯作者：
Park, Chan Hum
中科院分区：
文献类型：
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作者：
Park, Ye Ri;Sultan, Md. Tipu;Park, Chan Hum
丝素蛋白（SF）是一种被广泛研究的用于组织工程的生物材料，包括伤口愈合。然而，SF对这一现象影响的信号传导机制尚未确定。在本研究中，通过芯片分析，NF-kappa B信号的调控基因在sf处理的NIH3T3细胞中与其他基因一起被激活。免疫印迹分析证实NF-kappa B信号通路的激活是由于SF诱导IKK α、IKK β、p65的蛋白表达水平以及I kappa B α的降解。SF处理NIH3T3细胞也增加了cyclin D1、vimentin、纤维连接蛋白和血管内皮生长因子（VEGF）的表达。当NF-kappa B被药理学抑制剂Bay 11-7082抑制时，SF处理下这些因子的表达被取消。在伤口划伤实验中，IKK α和IKK β siRNA敲低NF-kappa B也抑制了sf诱导的NIH3T3细胞的伤口愈合反应。综上所述，这些结果表明，sf通过规范的nf - κ B信号通路，通过NIH3T3细胞调节cyclin D1、vimentin、纤维连接蛋白和VEGF的表达，诱导伤口愈合。通过对大鼠部分厚度切除伤口的体内研究，我们证明了sf通过nf - κ B调节的蛋白（包括细胞周期蛋白D1、纤维连接蛋白和VEGF）诱导伤口愈合。体外和体内数据表明，SF通过调节nf - κ B信号调节蛋白诱导伤口愈合。一个多世纪以来，丝素一直被有效地用作伤口治疗的敷料。然而，通过丝素蛋白进行伤口愈合的机制尚未得到阐明。在这里，我们报告了丝素蛋白在体外和体内诱导伤口愈合的关键机制。通过基因和蛋白水平分析，我们发现NF-kappa B信号通过调节靶蛋白来调节丝素诱导的伤口愈合。因此，NF-kappa B信号通路可作为丝素蛋白基生物材料的治疗靶点，用于伤口愈合和组织工程。(C) 2017材料学报Elsevier Ltd.出版。版权所有。
Silk fibroin (SF) is a well-studied biomaterial for tissue engineering applications including wound healing. However, the signaling mechanisms underlying the impact of SF on this phenomenon have not been determined. In this study, through microarray analysis, regulatory genes of NF-kappa B signaling were activated in SF-treated NIH3T3 cells along with other genes. Immunoblot analysis confirmed the activation of the NF-kappa B signaling pathway as SF induced protein expression levels of IKK alpha, IKK beta, p65, and the degradation of I kappa B alpha. The treatment of NIH3T3 cells with SF also increased the expression of cyclin D1, vimentin, fibronectin, and vascular endothelial growth factor (VEGF). The expression of these factors by SF treatment was abrogated when NF-kappa B was inhibited by a pharmacological inhibitor Bay 11-7082. Knockdown of NF-kappa B using siRNA of IKK alpha and IKK beta also inhibited the SF-induced wound healing response of the NIH3T3 cells in a wound scratch assay. Collectively, these results indicated that SF-induced wound healing through the canonical NF-kappa B signaling pathway via regulation of the expression of cyclin D1, vimentin, fibronectin, and VEGF by NIH3T3 cells. Using an in vivo study with a partial-thickness excision wound in rats we demonstrated that SF-induced wound healing via NF-kappa B regulated proteins including cyclin D1, fibronectin, and VEGF. The in vitro and in vivo data suggested that SF induced wound healing via modulation of NF-kappa B signaling regulated proteins.Statement of SignificanceSilk fibroin has been effectively used as a dressing for wound treatment for more than a century. However, mechanistic insight into the basis for wound healing via silk fibroin has not been elucidated. Here we report a key mechanism involved in silk fibroin induced wound healing both in vitro and in vivo. Using genetic- and protein-level analyses, NF-kappa B signaling was found to regulate silk fibroin-induced wound healing by modulating target proteins. Thus, the NF-kappa B signaling pathway may be utilized as a therapeutic target during the formulation of silk fibroin-based biomaterials for wound healing and tissue engineering. (C) 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.