Glutamic acid is the main excitatory neurotransmitter acting both in the brain and in peripheral tissues. Abnormal distribution of glutamic acid receptors occurs in skin hyperproliferative conditions such as psoriasis and skin regeneration; however, the biological function of glutamic acid in the skin remains unclear. Using ex vivo, in vivo and in silico approaches, we showed that exogenous glutamic acid promotes hair growth and keratinocyte proliferation. Topical application of glutamic acid decreased the expression of genes related to apoptosis in the skin, whereas glutamic acid increased cell viability and proliferation in human keratinocyte cultures. In addition, we identified the keratinocyte glutamic acid excitotoxic concentration, providing evidence for the existence of a novel skin signalling pathway mediated by a neurotransmitter that controls keratinocyte and hair follicle proliferation. Thus, glutamic acid emerges as a component of the peripheral nervous system that acts to control cell growth in the skin. These results raise the perspective of the pharmacological and nutritional use of glutamic acid to treat skin diseases.
Glutamic Acid/pharmacology , Hair Follicle/drug effects , Hair/drug effects , Skin Physiological Phenomena , Skin/drug effects , Animals , Apoptosis , Cell Line , Cell Proliferation , Computer Simulation , Drug Development , Fibroblasts/metabolism , Glutamic Acid/metabolism , Humans , Keratinocytes/cytology , Male , Mice , Protein Interaction Mapping , Regeneration , Signal Transduction , Skin/metabolism
