Glucocorticoid receptors, epidermal homeostasis and hair follicle differentiation

Glucocorticoid receptor and Klf4 co-regulate anti-inflammatory genes in keratinocytes

“…In the case of GR, overexpression results in resistance to epidermal inflammation and tumorigenesis (Budunova et al, 2003;Pérez, 2011), while loss provokes an increased sensitivity to inflammatory stressors and skin carcinogenesis Sevilla et al, 2013). Likewise, inducible deletion of Klf4 in the epidermis results in increased DMBA/TPA induced tumorigenesis (Li et al, 2012).…”

“…To better understand and treat skin diseases, the identification and study of factors which regulate both terminal differentiation and immune response is particularly relevant. Studies by us and others have shown that the Glucocorticoid Receptor (GR), a ligand-dependent transcription factor (TF), is one such factor, as when activated by glucocorticoids (GCs) it suppresses inflammatory processes and induces keratinocyte terminal differentiation (Pérez, 2011;Vandevyver et al, 2014). Indeed GCs are widely used to treat inflammatory skin diseases; however prolonged usage results in undesirable side effects, including skin thinning and delayed wound healing (Schoepe et al, 2006).…”

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

“…Novel profibrotic targets modulated by MR were recently identified, including enzymes such as myocardial lysyl oxidase involved in the maturation of procollagen (Lopez et al, 2009) or profibrotic molecules as cardiotrophin 1 CT1 (Lopez-Andres et al, 2008, 2011, galectin 3 (Gal3) (Calvier et al, 2013), or lipocalin 2, also referred as neutrophil gelatinase-activated lipocaline (NGAL) Latouche et al, 2012;Gilet et al, 2015). Indeed, gene inactivation of CT1 (Lopez-Andres et al, 2011), Gal3 (Calvier et al, 2013;, and lipocalin 2 (Tarjus et al, 2015c) blunted the cardiac remodeling and inflammation induced by mineralocorticoids in experimental mouse models.…”

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

“…This, along with the functional homology between MR and GR raised the question of whether some of the GC effects might be mediated by MR (Farman et al, 2010;Pérez, 2011;Farman and Nguyen, 2015). Very recently, Farman´s group demonstrated that topical application of a pharmacological MR antagonist partially reversed the GC-induced skin atrophy in human healthy skin (Maubec et al, 2015).…”

“…However, adverse effects caused by chronic GC treatments such as skin atrophy and delayed wound healing limit their therapeutic use (Schäcke et al, 2002;Cato et al, 2004;Pérez, 2011). While the crucial function of GR in skin pathophysiology has been widely characterized, the exact role of MR in this tissue deserves further study (Farman et al, 2010;Pérez, 2011;Farman and Nguyen, 2015).…”