Abstract
Merkel cells (MCs) are involved in mechanoreception, but several lines of evidence suggest that they may also participate in skin disorders through the release of neuropeptides and hormones. In addition, MC hyperplasias have been reported in inflammatory skin diseases. However, neither proliferation nor reactions to the epidermal environment have been demonstrated. We established a culture model enriched in swine MCs to analyze their proliferative capability and to discover MC survival factors and modulators of MC neuroendocrine properties. In culture, MCs reacted to bFGF by extending outgrowths. Conversely, neurotrophins failed to induce cell spreading, suggesting that they do not act as a growth factor for MCs. For the first time, we provide evidence of proliferation in culture through Ki-67 immunoreactivity. We also found that MCs reacted to histamine or activation of the proton gated/osmoreceptor TRPV4 by releasing vasoactive intestinal peptide (VIP). Since VIP is involved in many pathophysiological processes, its release suggests a putative regulatory role for MCs in skin disorders. Moreover, in contrast to mechanotransduction, neuropeptide exocytosis was Ca2+-independent, as inhibition of Ca2+ channels or culture in the absence of Ca2+ failed to decrease the amount of VIP released. We conclude that neuropeptide release and neurotransmitter exocytosis may be two distinct pathways that are differentially regulated.
Highlights
Merkel cells (MCs) are cutaneous neuroendocrine cells that are mainly found in touch-sensitive areas of the glabrous epidermis and outer root sheaths of hair follicles [1,2,3]
They are thought to participate in skin homeostasis through the release of bioactive molecules, but few reports have focused on the neuroendocrine properties of MCs
We developed a method for generating cultures enriched in porcine MCs
Summary
Merkel cells (MCs) are cutaneous neuroendocrine cells that are mainly found in touch-sensitive areas of the glabrous epidermis and outer root sheaths of hair follicles [1,2,3]. MCs are discerned from keratinocytes by their close connections to sensory neurons, the presence of dense-core neurosecretory granules and expression of cytokeratin (CK) 20. Their relationship with nerve terminals and their particular location have led to the hypothesis that MCs function in mechanoreception [4]. MCs produce bioactive amines and peptides such as serotonin, met-enkephalin, chromogranin A, calcitonin generelated peptide (CGRP) and vasoactive intestinal peptide (VIP), which are held in dense-core granules [12,13]. They belong to the neuroendocrine cell family. The role of MCs in the cutaneous environment remains largely unexplored
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