Adipokine-Enriched Adipose Extract Restores Skin Barrier and Ameliorates Inflammatory Dysregulation in Atopic Dermatitis Mice
Adipokine-Enriched Adipose Extract Restores Skin Barrier and Ameliorates Inflammatory Dysregulation in Atopic Dermatitis Mice
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DOI：
10.1097/prs.0000000000011154
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发表时间：
2024-10-01
影响因子：
3.6
通讯作者：
Lu，Feng
中科院分区：
文献类型：
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作者：
Guan，Jingyan;Feng，Jingwei;Lu，Feng
背景：特应性皮炎（AD）是一种世界范围内高发的慢性皮肤病，以皮肤屏障异常和免疫失调为特征。传统疗法通常受到副作用和高成本的限制。由于脂肪因子具有抗炎和修复的特性，越来越被认为是治疗皮肤病的有前途的药物。脂肪胶原蛋白片段（ACF）是一种新型的富含脂肪因子的产物，可能通过调节免疫微环境和修复皮肤屏障来缓解AD。方法：高速均质（10000 rpm/min, 1min）、离心（3000 g, 3min）提取脂肪组织中的ACF。卵清蛋白诱导AD雌性BALB/c小鼠（6周龄）皮内注射0.2 ml ACF或PBS（阴性对照），正常小鼠为正常对照组（n= 6）。在AD诱导期（第50天）后，评估皮炎严重程度、炎症指标（表皮厚度、浸润肥大细胞、th型细胞因子表达）和皮肤屏障相关指标（经皮失水[TEWL]、皮肤屏障相关蛋白表达）。acf衍生的生物活性成分也使用蛋白质组学分析进行评估。结果：acf衍生的脂肪因子含有抗炎、皮肤屏障和脂质生物合成相关成分。ACF治疗降低了AD皮肤的皮炎严重程度（6.2±1.8,p< 0.0001）、表皮厚度（25.7±12.8 μm, p= 0.0045）、肥大细胞浸润（31.3±12.4个细胞/场，p= 0.0475）和th型细胞因子表达（INF-γ、TNF-α、IL-4、IL-4R、IL-13和IL-17A， p< 0.05）。TEWL（29.8±13.8 g/m）h, p= 0.0306)，皮肤屏障相关蛋白表达（聚丝蛋白：14258±4375，p= 0.0162; loricrin: 6037±1728,p= 0.0010; claudin-1: 20043±6406,p= 0.0420; ZO-1: 4494±1114,p= 0.0134）也有所改善。结论：ACF通过改善炎症失调和皮肤屏障缺陷改善小鼠AD模型（图形摘要，Supplementary Digital Content 1）。需要在更高级的动物模型中进一步验证。
Background:Atopic dermatitis (AD) is a chronic dermatosis with high incidence worldwide characterized by skin barrier abnormalities and immune dysregulation. Conventional therapies are usually limited by side effects and high cost. Given the anti-inflammatory and repairing properties, adipokines are increasingly considered as promising therapeutic agents for dermatoses. Adipose collagen fragments (ACF), a novel adipokine-enriched product, may alleviate AD through modulating immune microenvironment and restoring skin barrier.Methods:ACF was extracted from adipose tissue via high-speed homogenization (10000 rpm/min, 1min) and centrifugation (3000 g, 3min). Ovalbumin-induced AD female BALB/c mice (6-week-old) were intradermally injected with 0.2 ml of ACF or PBS (negative control), with normal mice being set as normal control (n= 6). Dermatitis severity, inflammatory metrics (epidermal thickness, infiltrated mast cells, Th-type cytokines expression), and skin barrier-related metrics (transepidermal water loss [TEWL], skin barrier-related proteins expression) were evaluated after the AD induction period (day 50). ACF-derived bioactive components were also evaluated using proteomic analysis.Results:ACF-derived adipokines contained anti-inflammatory, skin barrier-and lipid biosynthesis-related components. ACF treatment decreased dermatitis severity (6.2±1.8, p< 0.0001), epidermal thickness (25.7±12.8 μm, p= 0.0045), infiltrated mast cells (31.3±12.4 cells/field, p= 0.0475), and Th-type cytokines expression (INF-γ, TNF-α, IL-4, IL-4R, IL-13, and IL-17A; p< 0.05) in AD skins. TEWL (29.8±13.8 g/m 2. h, p= 0.0306) and skin barrier-related proteins expression (filaggrin: 14258±4375, p= 0.0162; loricrin: 6037±1728, p= 0.0010; claudin-1: 20043±6406, p= 0.0420; ZO-1: 4494±1114, p= 0.0134) were also improved.Conclusions:ACF improved AD in murine model by ameliorating inflammatory dysregulation and skin barrier defects (Graphical abstract, Supplementary Digital Content 1). Further validation is needed in more advanced animal models.