Calcitonin Gene-Related Peptide Upregulates Melanogenesis and Enhances Melanocyte Dendricity via Induction of Keratinocyte-Derived Melanotrophic Factors

Abstract

It has recently been shown that cutaneous axon terminals and epidermal melanocytes make contact via chemical synapses in human skin and that calcitonin gene-related peptide (CGRP) induces melanocyte proliferation. To further clarify the effect of neuropeptides on the biology and morphology of melanocytes, especially with respect to melanogenesis and melanocyte dendricity, organ cultures of normal human skin and cultured melanocytes were exposed to various neuropeptides present in intraepidermal nerve endings. Of the neuropeptides examined, skin exposed to CGRP in organ culture showed increases in melanocyte number, epidermal melanin content, melanosome number, and degree of melanization. CGRP alone had no significant effect on melanogenesis of cultured melanocytes, whereas the addition of medium conditioned by CGRP-stimulated keratinocytes (CGRP-KCM) induced melanogenesis as indicated by biochemical assays of tyrosinase activity and melanin content. Furthermore, CGRP-KCM significantly enhanced melanocyte dendricity, a crucial factor affecting epidermal pigmentation. These findings suggest that keratinocytes produce and secrete some melanotrophic factors following stimulation with CGRP, which modulate growth, melanin synthesis, and dendricity of melanocytes. These data demonstrate intimate interactions between the cutaneous nervous system and melanocytes within the epidermal environment.

Neuronal Control of Skin Function: The Skin as a Neuroimmunoendocrine Organ

“…CGRP also induces melanocyte proliferation by upregulating melano-genesis and enhances melanocyte dendricity by inducing keratinocyte-derived melanotrophic factors (873). Interestingly, skin exposed to CGRP showed increases in melanocyte number, epidermal melanin content, melanosome number, and degree of melanization.…”

Inflammatory and Angiogenic Abnormalities in Diabetic Wound Healing: Role of Neuropeptides and Therapeutic Perspectives

“…CGRP also inhibits IL-2 production from T lymphocytes [171] and increases, in combination with SP, the levels of IL-1 , IL-6 and TNF-in human dental pulp fibroblasts and IL-1 and TNF-in macrophages [172,173]. CGRP can also stimulate the proliferation of keratinocytes, EC and melanocytes [164,174,175]. In CGRP knockout mice (CGRP-/-), angiogenesis and wound healing were impaired compared with those in wild-type mice, and a decrease in the release of VEGF from the wound granulation tissues was shown [101].…”

“…Nevertheless, administration of growth factors has been shown to promote healing by affecting all phases of wound healing. Several growth factors have been studied for the promotion of diabetic wound healing, such as FGF [177][178][179], VEGF [48,82], granulocyte colonystimulating factor [180][181][182], and hepatocyte growth factor [175,[183][184][185][186][187]. Despite high expectations in laboratory models of wound healing, growth factor delivery has shown to have a limited clinical success.…”

Neuropeptídeos na pele

“…A NEP localiza-se precisamente na camada basal da epiderme, endotélio de vasos e anexos (folículos pilosos, glândulas sebáceas e écrinas e bainha perineural de nervos), enquanto a ECA concentra-se mais na superfície luminal de vasos. A NEP tem sua presença estendida a todas as camadas da epiderme em feridas experimentais durante a cicatrização, sugerindo sua partici- 122,123,124 This reinforces evidence that there is a role played by SP and by CGRP, both neupação no processo e reforçando o papel da inflamação neurogênica na reparação tecidual. Os estudos com NEP sugerem que essas enzimas podem ser úteis no futuro, na abordagem de certas afecções cutâneas em que haja alteração da presença de neuropeptídeos.…”

“…Além disso, o CGRP parece ser capaz de induzir ceratinócitos a secretar fatores melanogênicos. 122,123,124 Isso reforça um papel desempenhado pela SP e pelo CGRP, ambos neuropeptídeos de origem neural, na resposta à irradiação UV, atuando junto a outros peptídeos produzidos na pele, como o hormô-nio melanócito-estimulante alfa (alfa-MSH) e demais derivados da proopiomelanocortina.…”