Significance of N-methyl-D-aspartate (NMDA) receptor-mediated signaling in human keratinocytes.
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.
Nahm
Walter K
WK
University of California, San Diego, School of Medicine and Veteran Affairs Medical Center, San Diego, California USA.
Philpot
Benjamin D
BD
Adams
Michelle M
MM
Badiavas
Evangelos V
EV
Zhou
Linda H
LH
Butmarc
Janet
J
Bear
Mark F
MF
Falanga
Vincent
V
D000814:Aniline Compounds; D002118:Calcium / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D002450:Cell Communication; D016764:Cell Polarity; D002478:Cells, Cultured; D005456:Fluorescent Dyes; D006801:Humans; D007150:Immunohistochemistry; D007231:Infant, Newborn; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D008297:Male; D018613:Microscopy, Confocal; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D015398:Signal Transduction; D012867:Skin / Q000166:cytology; D012878:Skin Neoplasms / Q000473:pathology; D023822:Tissue Engineering; D014945:Wound Healing; D014966:Xanthenes
D000814:Aniline Compounds; C409648:Fluo 4; D005456:Fluorescent Dyes; D016194:Receptors, N-Methyl-D-Aspartate; D014966:Xanthenes; D002118:Calcium