TY - JOUR
T1 - Vasoactive intestinal peptide (VIP) regulates human melanocyte biology and hair follicle pigmentation
AU - Bertolini, Marta
AU - Baehr, M.
AU - Sulk, M.
AU - Ponce Perez, Lourdes
AU - Hardman, Jonathan
AU - Bíró, T
AU - Tobin, D
AU - Paus, Ralf
N1 - Annual Meeting of the Society-for-Investigative-Dermatology (SID), Scottsdale, AZ, MAY 11-14, 2016
PY - 2016/5/1
Y1 - 2016/5/1
N2 - Exploratory pilot experiments in our lab(s) had raised the possibility that vasoactive intestinal peptide (VIP), a key immunoinhibitory neuropeptide released by perifollicular sensory nerve fibers, may be a novel modulator of human HF pigmentation. This hypothesis was followed-up in the current study. After showing that the VIP receptors, VPAC1 and VPAC2, are expressed at gene and protein level in human anagen hair bulbs, we investigated whether VIP (10-7M) modulates human HF pigmentation in situ and in isolated human HF melanocytes (HFiMc). VIP significantly increased both the number of intraepithelial c-Kit+ HF melanocytes (HFMc) in situ and intrafollicular c-Kit transcription. By contrast, VIP down-regulated SCF gene and protein expression in organ-cultured human HFs. Interestingly, c-Kit/gp100 double- immunostaining indicated that most of the VIP-induced c-Kit+ HFMc represent immature/amelanotic HFMc. Intriguingly, VIP up-regulated the total number of gp100+, MITF+, or p-MITF+ HFMc and promoted intrafollicular melanin production in situ. VIP also significantly stimulated melanogenesis in isolated human HFiMc, suggesting that it impacts directly on HFMc, but also slightly inhibited HFMc/HFiMc proliferation in situ and in vitro. Preliminary results obtained with specific antagonists suggested that VPAC1 and VPAC2 mediated the VIP effects on HFMc. Since microarray and qRT-PCR analyses showed an up-regulation of phosphodiesterase 4D7 transcription in VIP-treated HFs, VIP may regulate the cAMP level in HFMc, possibly by utilizing downstream pathways shared with α-MSH signaling. In summary, our results reveal VIP as a novel, complex and clinically-relevant neuroendocrine regulator of human HF pigmentation.
AB - Exploratory pilot experiments in our lab(s) had raised the possibility that vasoactive intestinal peptide (VIP), a key immunoinhibitory neuropeptide released by perifollicular sensory nerve fibers, may be a novel modulator of human HF pigmentation. This hypothesis was followed-up in the current study. After showing that the VIP receptors, VPAC1 and VPAC2, are expressed at gene and protein level in human anagen hair bulbs, we investigated whether VIP (10-7M) modulates human HF pigmentation in situ and in isolated human HF melanocytes (HFiMc). VIP significantly increased both the number of intraepithelial c-Kit+ HF melanocytes (HFMc) in situ and intrafollicular c-Kit transcription. By contrast, VIP down-regulated SCF gene and protein expression in organ-cultured human HFs. Interestingly, c-Kit/gp100 double- immunostaining indicated that most of the VIP-induced c-Kit+ HFMc represent immature/amelanotic HFMc. Intriguingly, VIP up-regulated the total number of gp100+, MITF+, or p-MITF+ HFMc and promoted intrafollicular melanin production in situ. VIP also significantly stimulated melanogenesis in isolated human HFiMc, suggesting that it impacts directly on HFMc, but also slightly inhibited HFMc/HFiMc proliferation in situ and in vitro. Preliminary results obtained with specific antagonists suggested that VPAC1 and VPAC2 mediated the VIP effects on HFMc. Since microarray and qRT-PCR analyses showed an up-regulation of phosphodiesterase 4D7 transcription in VIP-treated HFs, VIP may regulate the cAMP level in HFMc, possibly by utilizing downstream pathways shared with α-MSH signaling. In summary, our results reveal VIP as a novel, complex and clinically-relevant neuroendocrine regulator of human HF pigmentation.
U2 - 10.1016/j.jid.2016.02.705
DO - 10.1016/j.jid.2016.02.705
M3 - Meeting Abstract
SN - 0022-202X
VL - 136
SP - S117
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 5 Suppl 1
ER -
