Autophagy Has a Significant Role in Determining Skin Color by Regulating Melanosome Degradation in Keratinocytes
Autophagy Has a Significant Role in Determining Skin Color by Regulating Melanosome Degradation in Keratinocytes
复制标题
DOI：
10.1038/jid.2013.165
复制
发表时间：
2013-10-01
影响因子：
6.5
通讯作者：
Yoshimori, Tamotsu
中科院分区：
文献类型：
--
作者：
Murase, Daiki;Hachiya, Akira;Yoshimori, Tamotsu
表皮中的黑色素决定了与种族皮肤多样性相关的肤色的广泛变化。关于角质形成细胞中黑素体的损失存在种族差异，但这些差异的机制及其对肤色调节的贡献仍不清楚。在这里，我们探讨了自噬在确定皮肤颜色的参与，通过调节角质形成细胞中的黑素体降解。来自高加索人皮肤的角质形成细胞比来自非裔美国人（AA）皮肤的角质形成细胞表现出更高的自噬活性。此外，与AA皮肤衍生的角质形成细胞相比，高加索皮肤衍生的角质形成细胞中自噬活性沿着更高，高加索皮肤衍生的角质形成细胞对黑素体处理更敏感，如通过其增强的自噬活性所示，这可能反映了由于模型的局限性而导致的人表皮中的实质性机制。通过使用溶酶体抑制剂或对自噬相关蛋白质具有特异性的小干扰RNA（这对于自噬至关重要）处理，角质形成细胞中的黑素体积聚会加速。此外，与皮肤外观的改变一致，离体培养的人皮肤和体外培养的人皮肤替代品中的黑色素水平被自噬激活剂显著降低，并被抑制剂增强。总之，我们的数据表明，自噬通过调节角质形成细胞中的黑素体降解在肤色决定中起着关键作用，从而有助于肤色的种族多样性。
Melanin in the epidermis determines the wide variation in skin color associated with ethnic skin diversity. Ethnic differences exist regarding melanosome loss in keratinocytes, but the mechanisms underlying these differences, and their contribution to the regulation of skin color, remain unclear. Here, we explored the involvement of autophagy in determining skin color by regulating melanosome degradation in keratinocytes. Keratinocytes derived from Caucasian skin exhibit higher autophagic activity than those derived from African American (AA) skin. Furthermore, along with the higher autophagy activity in Caucasian skin derived keratinocytes compared with AA skin derived keratinocytes, Caucasian skin derived keratinocytes were more sensitive to melanosome treatment as shown by their enhanced autophagic activity, which may reflect the substantial mechanisms in the human epidermis owing to the limitations of the models. Melanosome accumulation in keratinocytes was accelerated by treatment with lysosomal inhibitors or with small interfering RNAs specific for autophagy-related proteins, which are essential for autophagy. Furthermore, consistent with the alterations in skin appearance, the melanin levels in human skin cultured ex vivo and in human skin substitutes in vitro were substantially diminished by activators of autophagy and enhanced by the inhibitors. Taken together, our data reveal that autophagy has a pivotal role in skin color determination by regulating melanosome degradation in keratinocytes, and thereby contributes to the ethnic diversity of skin color.