Fibronectin-Containing Extracellular Vesicles Protect Melanocytes against Ultraviolet Radiation-Induced Cytotoxicity
Fibronectin-Containing Extracellular Vesicles Protect Melanocytes against Ultraviolet Radiation-Induced Cytotoxicity
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DOI：
10.1016/j.jid.2015.08.001
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发表时间：
2016-05-01
影响因子：
6.5
通讯作者：
Cho, Eun-Gyung
中科院分区：
文献类型：
--
作者：
Bin, Bum-Ho;Kim, Dae-Kyum;Cho, Eun-Gyung
皮肤黑素细胞通过暴露于UV辐射而被激活以分泌含黑色素的黑素体，以保护皮肤免受UV诱导的损伤。尽管表皮不断更新，但黑素细胞的更新速度非常缓慢，它们可以长期存活。然而，暴露于紫外线辐射的黑素细胞的生存机制尚不清楚。在这里，我们研究了黑素细胞衍生的细胞外囊泡在黑素细胞存活中的作用。黑素细胞细胞外囊泡蛋白质组的网络分析确定了细胞外基质组分纤连蛋白在一个中央节点，和释放的纤连蛋白的细胞外囊泡的黑素细胞暴露于UVB辐射后增加。使用抗纤连蛋白中和抗体和细胞外囊泡分泌的特异性抑制剂，我们证明了富含纤连蛋白的细胞外囊泡参与UVB辐射后黑素细胞的存活。此外，我们观察到，在黄褐斑患者的色素沉着病变，黑素细胞周围的细胞外空间含有更多的纤维连接蛋白与正常皮肤相比，这表明纤维连接蛋白参与维持黑素细胞在病理条件下。总的来说，我们的研究结果表明黑素细胞分泌含有纤连蛋白的细胞外囊泡以增加其在UVB辐射后的存活率。这些数据提供了重要的洞察力，不断刺激的黑色素细胞可以保持在病理条件下，如黄褐斑。
Skin melanocytes are activated by exposure to UV radiation to secrete melanin-containing melanosomes to protect the skin from UV-induced damage. Despite the continuous renewal of the epidermis, the turnover rate of melanocytes is very slow, and they survive for long periods. However, the mechanisms underlying the survival of melanocytes exposed to UV radiation are not known. Here, we investigated the role of melanocyte-derived extracellular vesicles in melanocyte survival. Network analysis of the melanocyte extracellular vesicle proteome identified the extracellular matrix component fibronectin at a central node, and the release of fibronectin-containing extracellular vesicles was increased after exposure of melanocytes to UVB radiation. Using an anti-fibronectin neutralizing antibody and specific inhibitors of extracellular vesicle secretion, we demonstrated that extracellular vesicles enriched in fibronectin were involved in melanocyte survival after UVB radiation. Furthermore, we observed that in the hyperpigmented lesions of patients with melasma, the extracellular space around melanocytes contained more fibronectin compared with normal skin, suggesting that fibronectin is involved in maintaining melanocytes in pathological conditions. Collectively, our findings suggest that melanocytes secrete fibronectin-containing extracellular vesicles to increase their survival after UVB radiation. These data provide important insight into how constantly stimulated melanocytes can be maintained in pathological conditions such as melasma.