Melasma is a common acquired hyperpigmentary disorder occurring primarily in photo‐exposed areas and mainly affecting women of childbearing age. To decipher the role of sex hormones in melasma, this viewpoint reviews the effects of sex hormones on cutaneous cells cultured in monolayers, in coculture, in 3D models and explants in the presence or the absence of UV. The data show that sex steroid hormones, especially oestrogen, can modulate in vitro pigmentation by stimulating melanocytes and keratinocyte pro‐pigmentary factors, but not via fibroblast or mast cell activation. In vitro data suggest that oestrogen acts on endothelial cell count, which may in turn increase endothelin‐1 concentrations. However, data on explants revealed that sex steroid even at doses observed during pregnancy cannot induce melanogenesis alone nor melanosome transfer but that it acts in synergy with UVB. In conclusion, we hypothesize that in predisposed persons, sex steroid hormones initiate hyperpigmentation in melasma by amplifying the effects of UV on melanogenesis via direct effects on melanocytes or indirect effects via keratinocytes and on the transfer of melanosomes. They also help to sustain hyperpigmentation by increasing the number of blood vessels and, in turn, the level of endothelin‐1.

Significance: Although a role for β-adrenergic receptor (ADRB) in cancer progression was suggested a long time ago, our serendipitous observation of the propranolol efficacy in treating infantile hemangioma (IH) has driven attention in exploring the antitumor properties of β-blockers. We identified Aquaporine-1 (AQP1) as a player in antitumor propranolol response and as a histological marker of IH vascular structures including telocytes, which are dendritic cells that form a distinctive peripheral layer in IH. We conclude that IH sensitivity to propranolol may rely, at least in part, on a cross talk between lesional vascular cells and stromal telocytes.

Systemic sclerosis (SSc) is a complex autoimmune connective tissue disease combining inflammatory, vasculopathic and fibrotic manifestations. Skin features, which give their name to the disease and are considered as diagnostic as well as prognostic markers, have not been thoroughly investigated in terms of therapeutic targets. CCN proteins (CYR61/CCN1, CTGF/CCN2, NOV/CCN3 and WISP1‐2‐3 as CCN4‐5‐6) are a family of secreted matricellular proteins implicated in major cellular processes such as cell growth, migration, differentiation. They have already been implicated in key pathophysiological processes of SSc, namely fibrosis, vasculopathy and inflammation. In this review, we discuss the possible implication of CCN proteins in SSc pathogenesis, with a special focus on skin features, and identify the potential actionable CCN targets.

DDR1 and DDR2 are expressed in skin but their expression differs according to the skin compartment, epidermis, dermis, hypodermis and to the embryonic origin of the cells. In skin, it seems that during physiological processes such as wound healing or pathological processes such as tumorigenesis or systemic sclerosis development only one of the DDR is dysregulated. Furthermore, the altered DDR in pathological process is not necessarily the DDR implicated in basal homeostasis. Indeed, in epidermis, while DDR1 is the main DDR involved in melanocyte homeostasis, DDR2 seems to be the main DDR implicated in melanoma. On the contrary, in dermis, while DDR2 is necessary for normal wound healing, dysregulation of DDR1 is associated with abnormal wound healing leading to keloid. In conclusion, targeting DDR could be a therapeutic solution, however side effects have to be managed carefully.