IL-22R Ligands IL-20, IL-22, and IL-24 Promote Wound Healing in Diabetic db/db Mice.
IL-22R Ligands IL-20, IL-22, and IL-24 Promote Wound Healing in Diabetic db/db Mice.
复制标题
IL-22R配体IL-20，IL-22和IL-24促进糖尿病DB/DB小鼠的伤口愈合。
DOI：
10.1371/journal.pone.0170639
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Ouyang W
中科院分区：
文献类型：
--
作者：
Kolumam G;Wu X;Lee WP;Hackney JA;Zavala-Solorio J;Gandham V;Danilenko DM;Arora P;Wang X;Ouyang W
糖尿病足溃疡 (DFU) 是 II 型糖尿病患者的主要并发症之一，可导致截肢和发病。尽管临床上使用多种方法来帮助伤口闭合，但许多患者仍然缺乏足够的治疗。在这里，我们发现 IL-20 亚家族细胞因子在正常伤口愈合过程中上调。虽然该亚家族中的每种细胞因子在伤口愈合中都有多余的作用，但缺乏 IL-22R（IL-20、IL-22 和 IL-24 的共同受体链）的小鼠，伤口愈合显着延迟。此外，IL-20、IL-22 和 IL-24 都能够促进 II 型糖尿病 db/db 小鼠的伤口愈合。从机制上讲，与该模型中加速伤口愈合的其他生长因子（例如 VEGF 和 PDGF）相比，IL-22 独特地诱导了参与受伤皮肤的上皮再生、组织重塑和先天宿主防御机制的基因。有趣的是，在感染性糖尿病伤口模型中，IL-22 治疗显示出比 PDGF 或 VEGF 更优越的疗效。综上所述，我们的数据表明 IL-20 亚家族细胞因子，特别是 IL-20、IL-22 和 IL-24，可能为 DFU 患者提供治疗益处。
Diabetic foot ulcers (DFU) are one of the major complications in type II diabetes patients and can result in amputation and morbidity. Although multiple approaches are used clinically to help wound closure, many patients still lack adequate treatment. Here we show that IL-20 subfamily cytokines are upregulated during normal wound healing. While there is a redundant role for each individual cytokine in this subfamily in wound healing, mice deficient in IL-22R, the common receptor chain for IL-20, IL-22, and IL-24, display a significant delay in wound healing. Furthermore, IL-20, IL-22 and IL-24 are all able to promote wound healing in type II diabetic db/db mice. Mechanistically, when compared to other growth factors such as VEGF and PDGF that accelerate wound healing in this model, IL-22 uniquely induced genes involved in reepithelialization, tissue remodeling and innate host defense mechanisms from wounded skin. Interestingly, IL-22 treatment showed superior efficacy compared to PDGF or VEGF in an infectious diabetic wound model. Taken together, our data suggest that IL-20 subfamily cytokines, particularly IL-20, IL-22, and IL-24, might provide therapeutic benefit for patients with DFU.