| First Author | Bigas J | Year | 2020 |
| Journal | J Invest Dermatol | Volume | 140 |
| Issue | 10 | Pages | 1899-1908 |
| PubMed ID | 32199993 | Mgi Jnum | J:297473 |
| Mgi Id | MGI:6472802 | Doi | 10.1016/j.jid.2020.03.933 |
| Citation | Bigas J, et al. (2020) Epidermal Mineralocorticoid Receptor Inactivation Affects the Homeostasis of All Skin Layers in Chronologically Aged Mice. J Invest Dermatol 140(10):1899-1908 |
| abstractText | 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 beta-catenin signaling. These findings highlight the importance of epidermal MR in regulating cross-talk among skin compartments in naturally aged skin through GC and beta-catenin signaling pathways. |
