A synthetic connexin 43 mimetic peptide augments corneal wound healing.
A synthetic connexin 43 mimetic peptide augments corneal wound healing.
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DOI：
10.1016/j.exer.2013.07.001
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发表时间：
2013-10
影响因子：
3.4
通讯作者：
Potts JD
中科院分区：
文献类型：
--
作者：
Moore K;Bryant ZJ;Ghatnekar G;Singh UP;Gourdie RG;Potts JD
安全快速闭合伤口和撕裂伤的能力是再生医学的一个需要领域，对愈合广泛的组织和伤口有影响。使用体内角膜损伤模型，我们的研究应用了一种新开发的能够促进伤口愈合和上皮再生的肽。α-羧基末端1（α CT 1）肽是连接蛋白43（Cx43）C-末端的25个氨基酸肽，经修饰可促进细胞摄取。先前将α CT 1应用于猪模型中切除皮肤伤口的研究产生的组织具有总体减少的瘢痕组织水平和缩短的愈合时间。在先前的工作中，α CT 1的快速代谢导致了本研究中使用的缓释剂对伤口愈合率的研究。在这里，我们在浓缩的普朗尼克溶液中直接递送α CT 1，并在持续系统中使用聚合藻酸盐-聚-L-鸟氨酸（A-PLO）微胶囊。细胞毒性分析显示微胶囊处理的细胞损失最小。使用组织学和荧光显微镜进行的伤口愈合测量表明，与对照组相比，α CT 1微囊处理的大鼠角膜愈合时间显著缩短（88% vs. 38%）。RT-PCR分析表明，最初的上调，随后下调的基因角蛋白-19（Krt 19）。封闭小带1（ZO-1）表现出相反的下调，随后上调，而Cx43表现出双相反应。炎症指数表明，与Pluronic凝胶溶剂相比，α CT 1微囊处理的角膜炎症减少。这些结果表明，当以缓释系统应用时，α CT 1可作为有益的伤口愈合治疗。
The ability to safely and quickly close wounds and lacerations is an area of need in regenerative medicine, with implications toward healing a wide range of tissues and wounds. Using an in vivo corneal injury model, our study applied a newly developed peptide capable of promotion of wound healing and epithelial regeneration. The alpha-carboxy terminus 1 (αCT1) peptide is a 25 amino acid peptide from the C-terminus of connexin 43 (Cx43), modified to promote cellular uptake. Previous studies applying αCT1 to excisional skin wounds in porcine models produced tissues having an overall reduced level of scar tissue and decreased healing time. Rapid metabolism of αCT1 in previous work led to the investigation of extended release on wound healing rate used in this study. Here we delivered αCT1 both directly, in a concentrated pluronic solution, and in a sustained system, using polymeric alginate-poly-l-ornithine (A-PLO) microcapsules. Cell toxicity analysis showed minimal cell-loss with microcapsule treatment. Measurement of wound healing using histology and fluorescence microscopy indicated significant reduction in healing time of αCT1 microcapsule treated rat corneas compared with controls (88% vs. 38%). RT-PCR analysis showed an initial up regulation followed by down regulation of the gene keratin-19 (Krt19). Zonula occludens 1 (ZO-1) showed an opposite down regulation followed by an up regulation whereas Cx43 showed a biphasic response. Inflammatory indexes demonstrated a reduction in the inflammation of corneas treated with αCT1 microcapsules when compared with pluronic gel vehicle. These results suggest αCT1, when applied in a sustained release system, acts as a beneficial wound healing treatment.