Hyperalphalipoproteinemic scavenger receptor BI knockout mice exhibit a disrupted epidermal lipid barrier
Hyperalphalipoproteinemic scavenger receptor BI knockout mice exhibit a disrupted epidermal lipid barrier
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DOI：
10.1016/j.bbalip.2019.158592
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发表时间：
2020-03-01
影响因子：
4.8
通讯作者：
Van Eck, Miranda
中科院分区：
文献类型：
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作者：
Cardoso, Renata Martins;Creemers, Eline;Van Eck, Miranda
清道夫受体B类I型（SR-BI）介导高密度脂蛋白（HDL）对胆固醇酯（CE）的选择性摄取。SR-BI功能受损导致高脂蛋白血症，HDL部分运输的胆固醇水平升高。含载脂蛋白B （apoB）的脂蛋白中胆固醇的积累已被证明可以改变小鼠皮肤脂质组成和屏障功能。为了研究这些高胆固醇血症对皮肤的影响是否也发生在高脂蛋白血症中，我们比较了野生型和SR-BI基因敲除（SR-BI-/-）小鼠的皮肤。SR-BI缺乏不影响表皮胆固醇含量，仅引起神经酰胺亚类的微小变化。然而，表皮游离脂肪酸（FFA）池富含短链和不饱和链。血浆CE水平与表皮FFA C18:1含量密切相关。表皮游离脂肪酸的增加与胆固醇和游离脂肪酸合成基因的下调相一致，表明对血浆胆固醇和游离脂肪酸进入皮肤的通量增加有代偿反应。重要的是，SR-BI-/-表皮脂质屏障对乙基苯甲酸的渗透性增加，表明屏障功能受损。总之，SR-BI-/-小鼠高密度脂蛋白胆固醇水平的升高可以改变表皮脂质组成和脂质屏障功能，这与高胆固醇血症中由于载脂蛋白水平升高而观察到的情况类似。
Scavenger receptor class B type I (SR-BI) mediates the selective uptake of cholesteryl esters (CE) from high-density lipoproteins (HDL). An impaired SR-BI function leads to hyperalphalipoproteinemia with elevated levels of cholesterol transported in the HDL fraction. Accumulation of cholesterol in apolipoprotein B (apoB)-containing lipoproteins has been shown to alter skin lipid composition and barrier function in mice. To investigate whether these hypercholesterolemic effects on the skin also occur in hyperalphalipoproteinemia, we compared skins of wild-type and SR-BI knockout (SR-BI-/-) mice. SR-BI deficiency did not affect the epidermal cholesterol content and induced only minor changes in the ceramide subclasses. The epidermal free fatty acid (FFA) pool was, however, enriched in short and unsaturated chains. Plasma CE levels strongly correlated with epidermal FFA C18:1 content. The increase in epidermal FFA coincided with downregulation of cholesterol and FFA synthesis genes, suggesting a compensatory response to increased flux of plasma cholesterol and FFAs into the skin. Importantly, the SR-BI-/- epidermal lipid barrier showed increased permeability to ethyl-paraminobenzoic acid, indicating an impairment of the barrier function. In conclusion, increased HDL-cholesterol levels in SR-BI-/- mice can alter the epidermal lipid composition and lipid barrier function similarly as observed in hypercholesterolemia due to elevated levels of apoB-containing lipoproteins.