Melanocyte and nerve fiber cross-talk enhances UV-B-induced melanogenesis in human epidermis and is facilitated by semaphorin-4A

ABSTRACT: Epidermal melanocytes form synaptic-like contacts with cutaneous nerve fibers but the functional outcome of this connection remains elusive. In this pilot study, we used our fully humanized re-innervated skin organ culture model to investigate whether melanocyte-nerve fibers interaction play a role in UV-B-induced melanogenesis. UV-B-irradiation significantly enhanced melanin content and tyrosinase activity in re-innervated skin ex vivo compared to non-innervated controls, indicating that neuronal presence is essential for exacerbating pigmentation upon UV-B irradiation in long-term culture. Comparative transcriptomic analysis between laser-capture-microdissected melanocytes from freshly embedded human skin and published microarray data on in vitro primary melanocytes identified Semaphorin-4A (SEMA4A) as possible mediator of melanocyte-nerve fibers interactions. SEMA4A protein levels in Gp100+ epidermal melanocytes were significantly higher in re-innervated skin than in skin alone, and reduced by UV-B treatment. Analysis of melanocytes in vitro showed reduced SEMA4A protein expression 24h after UV-B-irradiation while SEMA4A secretion into the medium was increased. In sensory neurons, conditioned media (CM) from UV-B irradiated melanocytes stimulated tubulin expression and axon growth. Re-transfer of CM from neurons that received CM from melanocytes back to melanocytes resulted into significant increased melanin content only when the CM derived from neurons previously receiving CM from UV-B irradiated melanocytes. These findings highlight the importance of melanocyte-neuron interactions for UV-B-induced melanogenesis and suggest that secreted proteins (e.g. SEMA4A) can function as a novel target in the treatment of hypo- and hyperpigmentation disorders.

ORGANISM(S): Homo sapiens

PROVIDER: GSE271182 | GEO | 2024/12/31

REPOSITORIES: GEO