Mitochondrial dynamics regulate melanogenesis through proteasomal degradation of MITF via ROS-ERK activation
Mitochondrial dynamics regulate melanogenesis through proteasomal degradation of MITF via ROS-ERK activation
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DOI：
10.1111/pcmr.12298
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发表时间：
2014-11-01
影响因子：
4.3
通讯作者：
Cho, Dong-Hyung
中科院分区：
文献类型：
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作者：
Kim, Eun Sung;Park, So Jung;Cho, Dong-Hyung
为了深入了解肥大细胞产生的肝素在调节表皮稳态和皮肤色素沉着中的作用，我们研究了肝素对正常人表皮角质形成细胞（NHEK）中黑素体摄取和促炎反应的影响。我们用黑素体或荧光微球的摄取来定量NHEK的吞噬活性。肝素通过阻断PI 3 k/Akt和MEK/ERK信号通路抑制角质形成细胞的吞噬功能。事实上，肝素处理的NHEKs在吞噬过程中显示Akt和ERK的活化受损，而PI 3 k和MEK抑制剂显著抑制NHEKs对黑素体的摄取。此外，炎症标志物环氧化酶-2（考克斯-2）的表达和前列腺素E-2（PGE（2））的产生在吞噬过程中被诱导，而这些作用在肝素存在时被下调。提示肝素在人皮肤表皮中可能具有抗吞噬和抗炎作用。
To gain insight for the role of mast cell-produced heparin in the regulation of epidermal homeostasis and skin pigmentation, we have investigated the effect of heparin on melanosome uptake and proinflammatory responses in normal human epidermal keratinocytes (NHEKs). We quantified phagocytic activity of NHEKs with uptake of melanosomes or fluorescent microspheres. Heparin exhibited the inhibitory effect on keratinocyte phagocytosis through blocking PI3k/Akt and MEK/ERK signaling pathways. In fact, the heparin-treated NHEKs showed impaired activation of Akt and ERK during phagocytosis, whereas PI3k and MEK inhibitors significantly suppressed melanosome uptake by NHEKs. In addition, the inflammation marker cycloxygenase-2 (COX-2) expression and prostaglandin E-2 (PGE(2)) production were induced during phagocytosis, while these effects were downregulated in the presence of heparin. Our observations suggest that heparin may play an antiphagocytic and anti-inflammation role in epidermis of human skin.