Mannosylerythritol lipids ameliorate ultraviolet A-induced aquaporin-3 downregulation by suppressing c-Jun N-terminal kinase phosphorylation in cultured human keratinocytes
Mannosylerythritol lipids ameliorate ultraviolet A-induced aquaporin-3 downregulation by suppressing c-Jun N-terminal kinase phosphorylation in cultured human keratinocytes
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DOI：
10.4196/kjpp.2019.23.2.113
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发表时间：
2019-03-01
影响因子：
2
通讯作者：
Kim, Dae-Yong
中科院分区：
文献类型：
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作者：
Bae, Il-Hong;Lee, Sung Hoon;Kim, Dae-Yong
甘露糖脂（MEL）是糖脂，具有多种药理学功效。MEL还通过未知的潜在机制显示皮肤保湿功效。水通道蛋白-3（AQP 3）是一种有助于表皮的水稳态的膜蛋白，并且在紫外线（UV）照射皮肤后AQP 3表达的降低与皮肤水分的减少相关。没有以前的研究检查是否皮肤保湿效果的MEL可能通过AQP 3表达的调制。在这里，我们首次报道了MEL改善UVA诱导的培养的人表皮角质形成细胞（HaCaT角质形成细胞）中AQP 3的下调。我们的研究结果表明，UVA照射降低AQP 3的表达在蛋白质和信使RNA（mRNA）水平，但MEL治疗显着改善这些影响。我们的丝裂原活化蛋白激酶抑制剂的分析表明，磷酸化的c-Jun N-末端激酶（JNK），而不是细胞外信号调节激酶或p38，介导UVA诱导的AQP 3下调，MEL治疗显着抑制UVA诱导的JNK磷酸化。为了探索可能的机制，我们测试了MEL是否可以调节过氧化物酶增殖物激活受体γ（PPAR-gamma）的表达，PPAR-gamma是AQP 3表达的有效转录因子。有趣的是，UVA照射显著抑制了HaCaT角质形成细胞中PPAR-gamma的mRNA表达，而JNK抑制剂和MEL显著挽救了这种效果。综上所述，这些发现表明，MEL改善UVA诱导的AQP 3下调HaCaT角质形成细胞抑制JNK激活，阻止减少PPAR-gamma。总的来说，我们的研究结果表明，MEL可以作为一种潜在的成分，调节AQP 3的表达，以改善皮肤保湿UVA辐射诱导的损伤。
Mannosylerythritol lipids (MELs) are glycolipids and have several pharmacological efficacies. MELs also show skin-moisturizing efficacy through a yet-unknown underlying mechanism. Aquaporin-3 (AQP3) is a membrane protein that contributes to the water homeostasis of the epidermis, and decreased AQP3 expression following ultraviolet (UV)-irradiation of the skin is associated with reduced skin moisture. No previous study has examined whether the skin-moisturizing effect of MELs might act through the modulation of AQP3 expression. Here, we report for the first time that MELs ameliorate the UVA-induced downregulation of AQP3 in cultured human epidermal keratinocytes (HaCaT keratinocytes). Our results revealed that UVA irradiation decreases AQP3 expression at the protein and messenger RNA (mRNA) levels, but that MEL treatment significantly ameliorated these effects. Our mitogen-activated protein kinase inhibitor analysis revealed that phosphorylation of c-Jun N-terminal kinase (JNK), but not extracellular signal-regulated kinase or p38, mediates UVA-induced AQP3 downregulation, and that MEL treatment significantly suppressed the UVA-induced phosphorylation of JNK. To explore a possible mechanism, we tested whether MELs could regulate the expression of peroxidase proliferator-activated receptor gamma (PPAR-gamma), which acts as a potent transcription factor for AQP3 expression. Interestingly, UVA irradiation significantly inhibited the mRNA expression of PPAR-gamma in HaCaT keratinocytes, whereas a JNK inhibitor and MELs significantly rescued this effect. Taken together, these findings suggest that MELs ameliorate UVA-induced AQP3 downregulation in HaCaT keratinocytes by suppressing JNK activation to block the decrease of PPAR-gamma. Collectively, our findings suggest that MELs can be used as a potential ingredient that modulates AQP3 expression to improve skin moisturization following UVA irradiation-induced damage.