Significance of N-methyl-D-aspartate (NMDA) receptor-mediated signaling in human keratinocytes
Significance of N-methyl-D-aspartate (NMDA) receptor-mediated signaling in human keratinocytes
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DOI：
10.1002/jcp.20010
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发表时间：
2004-08-01
影响因子：
5.6
通讯作者：
Falanga, V
中科院分区：
文献类型：
--
作者：
Nahm, WK;Philpot, BD;Falanga, V
越来越多的数据表明，谷氨酸可能作为一种细胞信号分子在非神经组织，如皮肤。在这里，我们证明了人类角质形成细胞中存在功能性N-甲基-D-天冬氨酸（NMDA）型谷氨酸受体。NMDA受体表达强烈反映了细胞与细胞接触的程度。创伤使参与上皮再形成的角质形成细胞中NMDA受体的表达极化，并且上皮再形成的过程被NMDA受体活化抑制。我们还表明，鳞状细胞癌缺乏NMDA受体。我们的数据表明，钙离子通过NMDA受体进入影响角质形成细胞的增殖，分化和迁移的周期在上皮形成。此外，NMDA受体活化可能在接触介导的生长抑制中发挥作用，这是肿瘤病理学过程中不存在的。该受体可作为调节角质形成细胞行为和治疗皮肤疾病的药理学靶点。
Increasing data suggest that glutamate might act as a cell-signaling molecule in non-neuronal tissues such as the skin. Here we demonstrate the presence of functional N-methyl-D-aspartate (NMDA)-type glutamate receptors in human keratinocytes. NMDA receptor expression strongly reflects the degree of cell-to-cell contact. Wounding polarizes the expression of NMDA receptors in keratinocytes involved in re-epithelialization, and the process of re-epithelialization is inhibited by NMDA receptor activation. We also demonstrate that squamous cell carcinomas lack NMDA receptors. Our data suggest that Ca2+ entry through NMDA receptors influences the cycle of keratinocyte proliferation, differentiation, and migration during epithelialization. Moreover, NMDA receptor activation might play a role in contact-mediated inhibition of growth, a process that is absent during neoplastic pathology. This receptor may serve as a pharmacological target for modulating keratinocyte behavior and treating cutaneous disorders.