Kao Biological Science Laboratories, Haga, Tochigi, Japan.
Kao Biological Science Laboratories, Haga, Tochigi, Japan.
J Invest Dermatol. 2013 Oct;133(10):2416-2424. doi: 10.1038/jid.2013.165. Epub 2013 Apr 4.
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.
表皮中的黑色素决定了与种族多样性相关的肤色广泛差异。角质细胞中的黑素小体丧失存在种族差异，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，我们通过调节角质细胞中的黑素小体降解来探索自噬在决定肤色中的作用。与非洲裔美国人（AA）皮肤来源的角质细胞相比，白种人皮肤来源的角质细胞具有更高的自噬活性。此外，与 AA 皮肤来源的角质细胞相比，白种人皮肤来源的角质细胞具有更高的自噬活性，这表明白种人皮肤来源的角质细胞对黑素小体处理更敏感，这可能反映了人类表皮中的大量机制，这是由于模型的限制。溶酶体抑制剂处理或用特异性针对自噬相关蛋白的小干扰 RNA 处理可加速角质细胞中黑素小体的积累，这些蛋白对于自噬是必需的。此外，与皮肤外观的改变一致，在体外培养的人皮肤和人皮肤替代物中，自噬激活剂可显著降低黑色素水平，而抑制剂则可增强黑色素水平。综上所述，我们的数据表明，自噬通过调节角质细胞中的黑素小体降解在决定肤色中起着关键作用，从而导致肤色的种族多样性。
