Paracrine regulation of melanogenesis

Abstract

Melanocytes are generally characterized by the basic ability of melanin synthesis and transfer to adjacent keratinocytes. This constitutes an individual skin phenotype and provides epidermal protection from various stimuli, such as ultraviolet irradiation, through a complex process called melanogenesis, which can be regulated by autocrine or paracrine factors. Recent evidence has revealed the paracrine effects of keratinocytes on melanogenesis by secreting cytokines, including α-melanocyte stimulating hormone and endothelin-1. In addition to keratinocytes, there are other types of cells in the skin, such as fibroblasts and immune cells, which are also actively involved in the regulation of melanocyte behaviour through the production of paracrine factors. In addition, extracellular matrix proteins, which are secreted mainly by skin-resident cells, not only play direct roles in regulating melanocyte morphology and functions but also provide structural support between the epidermis and dermis to control the distribution of various secreted cytokines from keratinocytes and/or fibroblasts, which are potentially involved in the regulation of melanogenesis. Moreover, understanding the origin of melanocytes (neural crest cells) and the presence of nerve endings in the epidermis can reveal the intimate contact between melanocytes and cutaneous specific nervous system proteins. Melanocytes are associated with all these networks with corresponding receptors expressed on the cell surface. In this review, we provide an overview of recent advances in determining the intimate relationships between melanocytes and their surrounding elements, which provide insights into the complex nature of the regulation of melanogenesis.

Roles of inflammation factors in melanogenesis (Review)

“…The most well-known receptor on melanocytes that modulates their function is the melanocortin-1 receptor (Mc1r). When α-melanocyte-stimulating hormone (α-MSH) binds to Mc1-r on the membrane of melanocytes, it activates adenylate cyclase, increases intracellular caMP, activates PKa-caMP response element-binding protein (creB) pathway, and then increases MiTF, promoting melanogenesis (25)(26)(27)(28). Mc1r is also a major regulator of human pigmentation and is also a melanoma susceptibility gene (28).…”

“…2). Melanocytes interact with these surrounding cells by expressing corresponding receptors on the cell surface (27). in addition, studies have revealed that paracrine factors can provide a variety of mechanisms to activate dna repair mechanisms by activating different receptors and signaling pathways to maintain melanocyte homeostasis and prevent uV mutagenesis (28).…”

Bio‐derived hydroxystearic acid ameliorates skin age spots and conspicuous pores

“…In an attempt to provide greater insight into the potential mechanism of action of HSA, particularly on the potential paracrine effect of fibroblasts after treatment, on the expression of pore and age spot problems, we examined changes in secretome of fibroblasts (cell culture conditioned media), determined by mass spectrometry‐based proteomics, that might influence the fibroblasts in an autocrine fashion or keratinocytes or melanocytes in a paracrine fashion . Dermal fibroblasts play a key role in ECM formation and melanocyte pigmentation .…”

“…Secretion of melanogenic paracrine factors can also be derived from both keratinocytes and fibroblasts as a result of UV‐induced oxidative stress . Downregulation of genes involved in epidermal differentiation has also been reported in age spots as well as decreased expression of filaggrin and involucrin .…”

Keratinocyte desmoglein 1 regulates the epidermal microenvironment and tanning response

“…Since induction of pigment production and secretion in MCs is a crucial protective response in 139 the epidermis that can be regulated by paracrine signaling (Serre et al, 2018;Yuan and Jin, 2018), 140 we next tested MC pigment secretion following incubation with conditioned media from KCs with 141 normal or suppressed Dsg1 expression. MCs were grown for 7 days in a 1:1 mixture of MC media 142 and media conditioned by KCs days 3-5 after initiation of differentiation.…”