Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Department of Chemistry and Loker Hydrocarbon Research Institute, University of Southern California, Los Angeles, California.
Am J Pathol. 2021 Jun;191(6):1049-1063. doi: 10.1016/j.ajpath.2021.02.015. Epub 2021 Mar 6.
Tissue injury elicits an inflammatory response that facilitates host defense. Resolution of inflammation promotes the transition to tissue repair and is governed, in part, by specialized pro-resolving mediators (SPM). The complete structures of a novel series of cysteinyl-SPM (cys-SPM) were recently elucidated, and proved to stimulate tissue regeneration in planaria and resolve acute inflammation in mice. Their functions in mammalian tissue repair are of interest. Here, nine structurally distinct cys-SPM were screened and PCTR1 uniquely enhanced human keratinocyte migration with efficacy similar to epidermal growth factor. In skin wounds of mice, PCTR1 accelerated closure. Wound infection increased PCTR1 that coincided with decreased bacterial burden. Addition of PCTR1 reduced wound bacteria levels and decreased inflammatory monocytes/macrophages, which was coupled with increased expression of genes involved in host defense and tissue repair. These results suggest that PCTR1 is a novel regulator of host defense and tissue repair, which could inform new approaches for therapeutic management of delayed tissue repair and infection.
组织损伤会引发炎症反应，从而促进宿主防御。炎症的消退促进了组织修复的转变，部分受到专门的促解决介质（SPM）的控制。最近，人们阐明了一系列新型半胱氨酰 SPM（cys-SPM）的完整结构，并证明它们能够刺激涡虫的组织再生和缓解小鼠的急性炎症。它们在哺乳动物组织修复中的作用引起了人们的兴趣。在这里，筛选了九种结构不同的 cys-SPM，PCTR1 独特地增强了人角质形成细胞的迁移，其功效与表皮生长因子相似。在小鼠的皮肤伤口中，PCTR1 加速了伤口的闭合。伤口感染增加了 PCTR1，同时减少了细菌负担。添加 PCTR1 降低了伤口细菌水平，并减少了炎症性单核细胞/巨噬细胞，这与宿主防御和组织修复相关基因的表达增加有关。这些结果表明，PCTR1 是宿主防御和组织修复的新型调节剂，这可能为治疗延迟组织修复和感染提供新的方法。
