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Title

Epidermal mineralocorticoid receptor plays beneficial and adverse effects in skin and mediates glucocorticoid responses

AuthorsBoix, Julia; Sevilla, Lisa M. ; Sáez, Zara; Carceller, Elena; Pérez, Paloma
KeywordsGlucocorticoids
Mineralocorticoid receptor
Epidermal knock-out
Inflammation
Skin damage
Wounding
Issue Date25-Jul-2016
PublisherElsevier
CitationJournal of Investigative Dermatology 136(12):2417-2426 (2016)
AbstractGlucocorticoids (GCs) regulate skin homeostasis and combat cutaneous inflammatory diseases; however, adverse effects of chronic GC treatments limit their therapeutic use. GCs bind and activate the GC receptor and the mineralocorticoid receptor (MR), transcription factors that recognize identical hormone responsive elements. Whether epidermal MR mediates beneficial or deleterious GC effects is of great interest for improving GC-based skin therapies. MR epidermal knockout mice exhibited increased keratinocyte proliferation and differentiation and showed resistance to GC-induced epidermal thinning. However, crucially, loss of epidermal MR rendered mice more sensitive to inflammatory stimuli and skin damage. MR epidermal knockout mice showed increased susceptibility to phorbol 12-myristate 13-acetate-induced inflammation with higher cytokine induction. Likewise, cultured MR epidermal knockout keratinocytes had increased phorbol 12-myristate 13-acetate-induced NF-κB activation, highlighting an anti-inflammatory function for MR. GC-induced transcription was reduced in MR epidermal knockout keratinocytes, at least partially due to decreased recruitment of GC receptor to hormone responsive element-containing sequences. Our results support a role for epidermal MR in adult skin homeostasis and demonstrate nonredundant roles for MR and GC receptor in mediating GC actions.
Description10 páginas, 6 figuras. Contiene material suplementario
Publisher version (URL)http://dx.doi.org/10.1016/j.jid.2016.07.018
URIhttp://hdl.handle.net/10261/149414
DOI10.1016/j.jid.2016.07.018
ISSN0022-202X
E-ISSN1523-1747
Appears in Collections:(IBV) Artículos
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