The mineralocorticoid receptor as a novel player in skin biology: beyond the renal horizon?

Abstract

Abstract:The mineralocorticoid receptor (MR) and its ligand aldosterone regulate renal sodium reabsorption and blood pressure and much knowledge has been accumulated in MR physiopathology, cellular and molecular targets. In contrast, our understanding of this hormonal system in non-classical targets (heart, blood vessels, neurons, keratinocytes…) is limited, particularly in the mammalian skin. We review here the few available data that point on MR in the skin and that document cutaneous MR expression and function, based on mouse models and very limited observations in humans. Mice that overexpress the MR in the basal epidermal keratinocytes display developmental and post-natal abnormalities of the epidermis and hair follicle, raising exciting new questions regarding skin biology. The MR as a transcription factor may be an unexpected novel player in regulating keratinocyte and hair physiology and pathology. Because its activating ligand also includes glucocorticoids, that are widely used in dermatology, we propose that the MR may be also involved in the side-effects of corticoids, opening novel options for therapeutical intervention.

ST2 receptor invalidation maintains wound inflammation, delays healing and increases fibrosis

“…This shift is not only limited to T-cell responses, as macrophages have also been noted to adjust their responses based on ST2 expression, notably in sST2 (S10). sST2 is reported to act as a decoy receptor for IL-33, also with the ability to inhibit macrophage-dependant inflammation (9). This is most likely through IL-33-induced production of IL-4 and IL-13, which are polarizing agents for M2a differentiation in vitro (S11).…”

The mineralocorticoid receptor plays a transient role in mouse skin development

“…Human and mouse skin can synthesize GCs and key enzymes of steroid synthesis, acting as a functional hypothalamo-pituitary-adrenal axis to secure epidermal homeostasis (6,s2,s3). While our previous work demonstrated that GR is required for epidermal development and homeostasis (7,8,s4), much less is known regarding MR in this tissue (9). Remarkably, transgenic mice with keratinocyte-specific overexpression of either MR or GR (s5,s6) showed strong phenotypical similarities at birth including atrophic skin, reduced hair follicle number and impaired epidermal maturation.…”

Emerging Roles of the Mineralocorticoid Receptor in Pathology: Toward New Paradigms in Clinical Pharmacology

“…Evidence for MR expression in the human epidermis and hair follicle (as well as in sebaceous and sweat glands) is available but with limited knowledge of its cutaneous role (Kenouch et al, 1994;Zennaro et al, 1997;Farman et al, 2010). Glucocorticoids are efficient drugs to treat chronic inflammatory or autoimmune skin diseases.…”