BLT2 expression improves skin integrity and protects from alterations caused by hyperglycemia in type 2 diabetes.
BLT2 expression improves skin integrity and protects from alterations caused by hyperglycemia in type 2 diabetes.
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DOI：
10.1080/19381980.2016.1267078
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Valderas JP
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文献类型：
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作者：
Leguina-Ruzzi A;Valderas JP
2型糖尿病（T2 D）可能多年未被诊断出来，导致慢性高血糖产生并发症，如伤口愈合延迟。报告显示，BLT 2活化改善角质形成细胞迁移和伤口愈合，以及通过促进肌动蛋白聚合来保护表皮屏障。本研究的目的是阐明BLT 2表达在T2 D皮肤上皮完整性中的作用。为此，我们在模型中使用野生型（WT）和BLT 2敲除小鼠，其中通过使动物保持高脂肪（HF）饮食超过5周来诱导T2 D样表型。在平行的体外方法中，我们在低和高葡萄糖浓度下培养BLT 2转染的HaCaT细胞48小时。离体和体外评价结构、跨上皮阻力（TEER）、IL-1 β、IL-8或CXCL 2、MMP 9、丝聚蛋白、兜甲蛋白和角蛋白10（K10）。此外，在体外研究了伤口愈合（WH）。来自T2 D和BLT 2敲除小鼠的皮肤显示TEER和IL-1 β表达降低，而CXCL 2、MMP 9、聚丝蛋白、兜甲蛋白和K10表达增加。该结构表明表皮萎缩;然而，在保持HF饮食的BLT 2敲除小鼠中，皮肤受到显著影响。HaCaT-BLT 2细胞呈现为有组织的单层，并且与仅载体转染的HaCaT-Mock细胞相比显示出更高的TEER和伤口愈合。同样，在低和高葡萄糖条件下，皮肤炎症，基质降解和分化标志物的表达的变化不太严重比HaCaT-Mock细胞。我们的研究结果表明，BLT 2通过调节分化标志物、细胞因子和MMP 9来改善上皮的完整性和功能。此外，BLT 2减弱高葡萄糖水平的破坏作用，从而加速伤口愈合。
Type 2 diabetes (T2D) can go undiagnosed for years, leading to a stage where chronic high blood sugar produces complications such as delayed wound healing. Reports have shown that BLT2 activation improves keratinocyte migration and wound healing, as well as protecting the epidermal barrier through the promotion of actin polymerization. The goal of this study was to elucidate the role of BLT2 expression in skin epithelial integrity in T2D. For this purpose, we used both wild type (WT) and BLT2 knockout mice in a model, in which a T2D-like phenotype was induced by keeping the animals on a high fat (HF) diet over 5 weeks. In a parallel in vitro approach, we cultured BLT2-transfected HaCaT cells at both low and high glucose concentrations for 48 h. Structure, transepithelial resistance (TEER), IL-1ß, IL-8 or CXCL2, MMP9, Filaggrin, Loricrin and Keratin 10 (K10) were evaluated ex vivo and in vitro. Additionally, wound healing (WH) was studied in vitro. The skin from T2D and BLT2 knockout mice showed a reduction in TEER and the expression of IL-1ß, and in increase in CXCL2, MMP9, Filaggrin, Loricrin and K10 expression. The structure suggested an atrophic epidermis; however, the skin was dramatically affected in the BLT2 knockout mice kept on a HF diet. HaCaT-BLT2 cells presented as an organized monolayer and showed higher TEER and wound healing compared with vector only-transfected HaCaT-Mock cells. Likewise, alterations in the expression of skin inflammatory, matrix degradation and differentiation markers under low and high glucose conditions were less severe than in HaCaT-Mock cells. Our results suggest that BLT2 improves epithelial integrity and function by regulating differentiation markers, cytokines and MMP9. Furthermore, BLT2 attenuates the damaging effects of high glucose levels, thereby accelerating wound healing.