Epidermal Mineralocorticoid Receptor Inactivation Affects the Homeostasis of All Skin Layers in Chronologically Aged Mice
Year: 2020
Type: article
Abstract: The increased production of endogenous glucocorticoids (GCs) in the skin of the elderly population contributes to age-related defects strikingly similar to those occurring after pharmacologic treatments with GCs. GCs act through the ligand-dependent transcription factors GC receptor (GR) and mineralocorticoid receptor (MR). We reported that epidermal MR plays nonredundant roles relative to GR in adult mouse skin homeostasis; however, its relative contribution to natural skin aging has not been previously investigated. A 13-month-old MR epidermal knockout (MR EKO ) mice showed differential features of aging relative to controls (CO) in all skin compartments. MR EKO mice were resistant to age-induced epidermal atrophy but showed reduced dermal thickness, with decreased collagen deposition and decreased SMAD2 and 3 activity. Importantly, the dermal white adipose tissue (dWAT) was 2.5-fold enlarged in 13-month MR EKO versus CO, featuring adipocyte hyperplasia and hypertrophy at least in part through early increases in Pparg . These changes correlated with compartment-specific alterations in GC signaling. In addition, conditioned medium from MR EKO keratinocytes increased adipocyte differentiation, indicating paracrine regulation of adipogenesis through mechanisms that include activation of β-catenin signaling. These findings highlight the importance of epidermal MR in regulating cross-talk among skin compartments in naturally aged skin through GC and β-catenin signaling pathways.
Authors: Judit Bigas, Lisa M. Sevilla, Paloma Pérez
Language: English
Topic: Skin Protection and Aging
Subfield: Dermatology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,400
OpenAlex ID: W3012402156