Significance of N‐methyl‐d‐aspartate (NMDA) receptor‐mediated signaling in human keratinocytes

Abstract

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.

Glutamatergic Signaling Maintains the Epithelial Phenotype of Proximal Tubular Cells

“…In addition, activation of NMDAR decreases basal actin polymerization state and TGF-␤1-induced actin reorganization in HK-2. The effect of NMDAR activation and Ca 2ϩ on cell migration 19,20 and actin organization 26,27 has previously been reported in different cell types. Nahm et al 20 showed that Ca 2ϩ entry through activated NMDAR inhibited keratinocyte outgrowth and migration.…”

“…The effect of NMDAR activation and Ca 2ϩ on cell migration 19,20 and actin organization 26,27 has previously been reported in different cell types. Nahm et al 20 showed that Ca 2ϩ entry through activated NMDAR inhibited keratinocyte outgrowth and migration. Kihara et al 19 reported that stimulation of NMDAR inhibited neuronal migration in embryonic rat cerebral cortex.…”

“…25 Indeed, NMDAR activation has been shown to induce changes in actin organization in cerebellar granule cells 26 and retinal neurons 27 and to inhibit cell migration in neurons 19 and keratinocytes. 20 Taking into consideration knowledge of multiple characteristics of NMDAR in a variety of tissues, including renal itself, we sought to examine its role in the maintenance of the epithelial phenotype of proximal tubular epithelial cells (PTECs) and in tubular EMT in vitro. Furthermore, we examined the role of channel activation in tubulointerstitial fibrosis induced by UUO in mice.…”

Topical Phenytoin in Neuralgic Pain, Peripheral Modulation of Central Sensitization: Two Case Reports

“…Phenytoin attenuates α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated depolarizations by the agonists AMPA and quisqualate in mM concentration range, but is not able to fully antagonize responses to NMDA at concentrations less than 100 mM. Ionotropic glutamate receptors of the NMDA receptor type are expressed on keratinocytes [53,54]. Phenytoin could effectively decrease the synaptic excitation through influencing the NMDA receptor [45].…”

Avaliação da cicatrização cutânea: fluorescência e estereologia

“…Em resumo, através da análise do processo de cicatrização da pele, podese concluir que: a) a maioria dos achados macroscópicos e sob lente de aumento (20 X) são corroborados pelos achados vistos ao microscópio de luz; b) na fase proliferativa, observa-se a promoção do evento em todos os tecidos epiteliais (camadas córnea, epidérmica e anexos cutâneos); c) as etapas ou eventos da cicatrização da pele (coagulação, inflamação, proliferação e remodelação) ocorreram, em parte do tempo, de forma simultânea, de acordo com os achados da literatura (Mokrý et al, 2006) (Nahm et al, 2004). Apesar disso, a determinação ou quantificação de moléculas não foi abordada no presente trabalho.…”