Derivatives of gecko cathelicidin-related antioxidant peptide facilitate skin wound healing
Derivatives of gecko cathelicidin-related antioxidant peptide facilitate skin wound healing
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壁虎导管素相关抗氧化肽衍生物促进皮肤伤口愈合
DOI：
10.1016/j.ejphar.2020.173649
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发表时间：
2021-01-05
影响因子：
5
通讯作者：
Wang, Guannan
中科院分区：
文献类型：
--
作者：
Cai, Shasha;Lu, Changao;Wang, Guannan
Cathelicidins 是宿主防御系统中一类基因编码的多功能因子。它们最近作为有前途的候选药物引起了极大的关注。导管素在脊椎动物中得到了充分研究，但尚未有关于壁虎导管素的研究报道。最近，我们从壁虎中鉴定出一种新型的抗菌素，Gj-CATH3。与大多数导管素不同，Gj-CATH3 在体外表现出有效的抗氧化活性。不幸的是，轻微的毒性和较高的合成成本限制了其应用。因此，我们设计了一系列 GjCATH3 类似物，用于开发具有改善的细胞选择性的短肽。功能分析表明，两种截短肽，Gj-CATH3-(38-42)-肽和Gj-CATH3-(33-42)-肽，对ABTS和DPPH自由基表现出优异的抗氧化活性。此外，与Gj-CATH3相比，细胞毒性和溶血活性明显较低。有趣的是，这两种肽还在全层皮肤伤口的小鼠模型中表现出显着的伤口愈合特性。这些肽可诱导 HaCaT 细胞增殖，并防止受伤皮肤组织中 SOD 活性降低和 MDA 浓度增加。该报告是第一份涉及爬行动物中具有有效伤口愈合活性的抗菌素的报告。我们的研究将丰富人们对cathelicidin生物学功能的认识，并为其临床应用提供理论基础。
Cathelicidins are a class of gene-encoded multifunctional factors in host defence systems. They have recently attracted a great deal of attention as promising drug candidates. Cathelicidins are well studied in vertebrates, yet no studies have been reported concerning gecko cathelicidin. Recently, we identified a novel cathelicidin from Gekko japonicas, Gj-CATH3. Unlike most cathelicidins, Gj-CATH3 exhibits potent antioxidant activity in vitro. Unfortunately, slight toxicity and high synthesis cost restrict its application. Thus, we designed a series of GjCATH3 analogues for development of short peptides with improved cell selectivity. Functional analysis showed that two truncated peptides, Gj-CATH3-(38-42)-peptide and Gj-CATH3-(33-42)-peptide, exhibited excellent antioxidant activity against ABTS and DPPH free radicals. Further, cytotoxicity and hemolytic activities were observably lower compared to Gj-CATH3. Interestingly, both peptides also demonstrate significant wound healing properties in a mouse model with full-thickness skin wounds. The peptides induce HaCaT cell proliferation and prevent decreases in SOD activity and increases of MDA concentration in injured-skin tissue. This report is the first to address cathelicidin from reptilia that exhibit potent wound healing activity. Our research will enrich understanding of cathelicidin biological functions, and provide a theoretical basis for its clinical application.