Tuesday, 21 November 2017
ANIMAL MODELS OF SKIN PATHOLOGIES UNIT  

 

  In mammals, the epidermis –the epithelial compartment of the skin formed during the embryogenesis– acts as a barrier between the individual and the environment, and needs to be maintained during adult life for survival. The importance of hormonal regulation for the skin is evidenced by numerous endocrine abnormalities with cutaneous manifestations, including disorders of the epidermal barrier and hair function. Hormone action is mediated by members of the nuclear receptor (NR) superfamily, which are ligand-activated transcription factors that integrate multiple cellular processes. In fact, NRs are the most targeted molecules for the treatment of skin diseases, which are highly prevalent in humans, representing a socio-economic burden. Many skin disorders feature chronic inflammation, and non-melanoma skin cancer constitutes the most common epithelial cancer.

  The glucocorticoid (GC) receptor (GR) belongs to the NR superfamily and regulates gene expression through DNA-binding–dependent and –independent mechanisms. GR is ubiquitously expressed and mediates the biological and therapeutical effects of endogenous and synthetic GCs. The wide use of GC analogs in clinical practice relies on their great efficacy as anti-inflammatory agents, mostly due to the antagonism between ligand-activated GR and the pro-inflammatory NF-kappaB and MAPK/AP-1 signaling pathways in many cell types. However, and despite the great efficacy of GC-based treatments, the use of high doses of these compounds and/or their long-term use in patients cause severe undesired side-effects (including diabetes, osteoporosis and delayed wound healing) as well as GC-resistance. It is thus necessary deciphering the molecular mechanisms underlying GR therapeutical actions to design improved GC-based therapies for treating cutaneous diseases.

  Our group has contributed to a better understanding of the role of GR in skin pathophysiology through the generation and characterization of genetically modified mice with GR gain- and loss-of-function. Our results demonstrate that GR is required for normal epidermal development as well as adult skin homeostasis, having identified GR-target genes that participate in epidermal maturation as well as immune response. Remarkably, many of the identified genes are also dysregulated in inflammatory skin diseases such as atopic dermatitis and psoriasis, thus establishing a link between GR, skin barrier defects and cutaneous inflammation.

  Given that mineralocorticoid receptor (MR) can bind GCs with high affinity, as well as modulate transcriptional activity by itself or in combination with GR, we have expanded our interests to analyze MR function in cutaneous biology by multidisciplinary in vivo and in vitro approaches.

 

 

 rPrincipal Investigator:

 Paloma Pérez

 
 
Currículum Vitae

Publications

Teléfono: 963391766

Email: pperezibv.csic.es

 
     
 
  • Pérez Sánchez, Paloma
  • Bigas Coromina, Judit
  • Sevilla , Lisa