Role of PPAR, LXR, and PXR in epidermal homeostasis and inflammation

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Isolation and Culture of Primary Mouse Keratinocytes from Neonatal and Adult Mouse Skin
10:51

Isolation and Culture of Primary Mouse Keratinocytes from Neonatal and Adult Mouse Skin

Published on: July 14, 2017

31.7K

Matthias Schmuth1, Verena Moosbrugger-Martinz1, Stefan Blunder1

  • 1Department of Dermatology and Venereology, Innsbruck Medical University, Innsbruck, Austria.

Biochimica Et Biophysica Acta
|December 10, 2013
PubMed

Insights

Nuclear hormone receptors (NHR) regulate epidermal lipids. Ligands for peroxisome proliferator-activated receptor (PPAR), liver X receptor (LXR), and pregnane X receptor (PXR) show therapeutic potential for skin diseases.

Area of Science:

  • Dermatology
  • Molecular Biology
  • Biochemistry

Background:

  • Epidermal lipid metabolism is intrinsically linked to nuclear hormone receptors (NHRs).
  • NHRs are a large superfamily of transcription factors, with a subgroup acting as ligand-activated heterodimers with retinoid X receptor.
  • Key NHRs in skin include peroxisome proliferator-activated receptor (PPAR), liver X receptor (LXR), and pregnane X receptor (PXR).

Purpose of the Study:

  • To explore the role of NHRs in epidermal lipid metabolism and their therapeutic implications in skin conditions.
  • To investigate how NHR activation influences keratinocyte function and the cutaneous immune system.
  • To highlight the potential of PPAR, LXR, and PXR ligands as therapeutic targets in dermatology.

Main Methods:

  • Review of existing literature on NHRs, epidermal lipids, and skin biology.
  • Analysis of the functions of PPAR, LXR, and PXR in keratinocytes and the immune system.
  • Examination of the impact of NHR ligand activation on gene transcription and cellular processes.

Main Results:

  • Ligand activation of PPARs and LXRs in keratinocytes promotes differentiation, lipid accumulation, and epidermal barrier repair.
  • Activation of PPAR, LXR, and PXR in the cutaneous immune system exhibits inhibitory effects, partly via NF-kappaB pathway downregulation.
  • PXR activation demonstrates antifibrotic properties in the skin through inhibition of TGF-beta.

Conclusions:

  • Ligands targeting PPAR, LXR, and PXR offer significant therapeutic benefits for various skin diseases.
  • These NHRs and their ligands represent promising therapeutic avenues for future dermatological treatments.
  • Understanding the interplay between epidermal lipids and NHRs is crucial for developing novel skin therapies.
Keywords:
DifferentiationHormoneKeratinocyteLipidSkin barrierStratum corneum

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