Epidermal nerve fibers modulate keratinocyte growth via neuropeptide signaling in an innervated skin model.
J Invest Dermatol
; 133(6): 1620-8, 2013 Jun.
Article
em En
| MEDLINE
| ID: mdl-23283070
ABSTRACT
Atopic eczema is a chronic inflammatory skin disease characterized by cutaneous nerve fiber sprouting and epidermal hyperplasia, pointing to an involvement of the peripheral nervous system in cutaneous homeostasis. However, the interaction of sensory neurons and skin cells is poorly understood. Using an innervated skin model, we investigated the influence of sensory neurons on epidermal morphogenesis. Neurons induced the proliferation of keratinocytes, resulting in an increase in the epidermal thickness. Inhibition of calcitonin gene-related peptide (CGRP), but not substance P (SP) signaling, reversed this effect. Human CGRP enhanced keratinocyte proliferation and epidermal thickness in skin models, demonstrating a key role of CGRP in modulating epidermal morphogenesis, whereas SP had only a moderate effect. Innervated skin models composed of atopic skin cells showed increased neurite outgrowth, accompanied by elevated CGRP release. As atopic keratinocytes were sensitized to CGRP owing to higher expression levels of the CGRP receptor components, receptor activity-modifying protein 1 (RAMP1) and receptor component protein (RCP), atopic innervated skin models displayed a thicker epidermis than did healthy controls. We conclude that neural CGRP controls local keratinocyte growth. Our results show that the crosstalk of the cutaneous peripheral nervous system and skin cells significantly influences epidermal morphogenesis and homeostasis in healthy and atopic skin.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neuropeptídeos
/
Queratinócitos
/
Dermatite Atópica
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Epiderme
/
Células Epidérmicas
Tipo de estudo:
Prognostic_studies
Limite:
Adult
/
Humans
/
Middle aged
Idioma:
En
Revista:
J Invest Dermatol
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Alemanha