Localization of serine racemase and its role in the skin.

Localization of serine racemase and its role in the skin.
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DOI:
10.1038/jid.2014.22
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发表时间:
2014-06
影响因子:
6.5
通讯作者:
Mori, Hisashi
Mori, Hisashi
中科院分区:
医学1区
文献类型:
--
作者:
Inoue, Ran;Yoshihisa, Yoko;Tojo, Yosuke;Okamura, Chieko;Yoshida, Yuzo;Kishimoto, Jiro;Luan, Xinghua;Watanabe, Masahiko;Mizuguchi, Mineyuki;Nabeshima, Yuko;Hamase, Kenji;Matsunaga, Kenji;Shimizu, Tadamichi;Mori, Hisashi

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D-丝氨酸是中枢神经系统N-甲基-D-天冬氨酸(NMDA型)型谷氨酸受体的内源性协同激动剂,其合成由丝氨酸消旋酶(SR)催化。近年来,研究发现NMDA受体表达于皮肤角质形成细胞,参与角质形成细胞的生长和分化调控。然而,SR在皮肤中的定位和作用仍不清楚。在这里,我们以SR-KO小鼠为对照,证明了SR蛋白在野生型(WT)小鼠表皮颗粒层和角化层的定位及其在融合的WT KC中的出现。我们还证明了表皮KCs中存在将L-丝氨酸转化为D-丝氨酸的机制。此外,我们还发现成年SR-KO小鼠表皮KCs分化相关基因表达水平升高,出生后第5天SR-KO小鼠表皮屏障功能和超微结构发生变化。我们的发现表明,皮肤表皮中的SR参与了表皮KCs的分化和皮肤屏障的形成。
D-Serine is an endogenous coagonist of the N-methyl-D-aspartate (NMDA)–type glutamate receptor in the central nervous system and its synthesis is catalyzed by serine racemase (SR). Recently, the NMDA receptor has been found to be expressed in keratinocytes (KCs) of the skin and involved in the regulation of KC growth and differentiation. However, the localization and role of SR in the skin remain unknown. Here, using SR-knockout (SR-KO) mice as the control, we demonstrated the localization of the SR protein in the granular and cornified layer of the epidermis of wild-type (WT) mice and its appearance in confluent WT KCs. We also demonstrated the existence of a mechanism for conversion of L-serine to D-serine in epidermal KCs. Furthermore, we found increased expression levels of genes involved in the differentiation of epidermal KCs in adult SR-KO mice, and alterations in the barrier function and ultrastructure of the epidermis in postnatal day 5 SR-KO mice. Our findings suggest that SR in the skin epidermis is involved in the differentiation of epidermal KCs and the formation of the skin barrier.
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