Biosynthesis of D-Series Resolvins in Skin Provides Insights into their Role in Tissue Repair.
Biosynthesis of D-Series Resolvins in Skin Provides Insights into their Role in Tissue Repair.
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DOI：
10.1016/j.jid.2018.03.1498
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发表时间：
2018-09
期刊：
影响因子：
--
通讯作者：
Spite M
中科院分区：
文献类型：
--
作者：
Hellmann J;Sansbury BE;Wong B;Li X;Singh M;Nuutila K;Chiang N;Eriksson E;Serhan CN;Spite M
皮肤损伤会导致潜在的组织损伤，必须快速修复，以尽量减少与病原体的接触并恢复屏障功能。虽然生长因子在组织修复中的作用已确定，但脂质介质在皮肤修复中的作用尚未得到广泛研究。使用基于质谱的脂质介质代谢组学方法，我们鉴定了小鼠和猪皮肤损伤期间的 D 系列解析素和相关的促解析脂质介质。人表皮角质形成细胞的分化增加了 15-脂氧合酶的表达和 17S-羟基二十二碳六烯酸的立体特异性产生，17S-羟基二十二碳六烯酸是常见的上游生物合成标记物和 D 系列分解素的前体。在人和猪的皮肤中，D系列分解素的特异性受体在表皮层中表达，而RvD1受体Alx/Fpr2缺陷的小鼠在上皮再生方面表现出内源性缺陷。局部应用 D 系列消退素可加速皮肤损伤期间的上皮再形成，并以受体依赖性方式增强人表皮角质形成细胞的迁移。 RvD2 对再上皮化的增强作用在其受体遗传缺陷的小鼠中消失，并且用 RvD2 刺激的角质形成细胞的迁移与 PI3K-AKT-mTOR-S6 途径的激活有关，该途径的阻断阻止了其促迁移作用。总的来说，这些结果表明解析素在组织修复程序中具有直接作用。
Cutaneous injury causes underlying tissue damage that must be quickly repaired to minimize exposure to pathogens and to restore barrier function. While the role of growth factors in tissue repair is established, the role of lipid mediators in skin repair has not been extensively investigated. Using a mass spectrometry-based lipid mediator metabolomics approach, we identified D-series resolvins and related pro-resolving lipid mediators during skin injury in mice and pigs. Differentiation of human epidermal keratinocytes increased expression of 15-lipoxygenase and stereospecific production of 17S-hydroxydocosahexaenoic acid, the common upstream biosynthetic marker and precursor of D-series resolvins. In human and pig skin, specific receptors for D-series resolvins were expressed in the epidermal layer and mice deficient in RvD1 receptor Alx/Fpr2 showed an endogenous defect in re-epithelialization. Topical application of Dseries resolvins expedited re-epithelialization during skin injury and they enhanced migration of human epidermal keratinocytes in a receptor-dependent manner. The enhancement of re-epithelialization by RvD2 was lost in mice genetically-deficient in its receptor and migration of keratinocytes stimulated with RvD2 was associated with activation of the PI3K-AKT-mTOR-S6 pathway, blockade of which prevented its pro-migratory actions. Collectively, these results demonstrate that resolvins have direct roles in the tissue repair program.
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影响因子：
5.5
作者：
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发表时间：
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影响因子：
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