Basis for improved permeability barrier homeostasis induced by PPAR and LXR activators: Liposensors stimulate lipid synthesis, lamellar body secretion, and post-secretory lipid processing

Mao Qiang Man, Eung Ho Choi, Matt Schmuth, Debra Crumrine, Yoshikazu Uchida, Peter M. Elias, Walter M. Holleran, Kenneth R. Feingold

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

Previously, we demonstrated that topical applications of peroxisome proliferator-activated receptors (PPARs) and liver X receptor (LXR) activators improve permeability barrier homeostasis. We showed further that stimulation of epidermal differentiation provides one mechanism that could account for such improvement. Here, we studied the effects of these agents on the lipid matrix of the stratum corneum. Hairless mice were treated topically with activators of PPARα (WY14643), PPARδ (GW1514), PPARγ (ciglitazone), and LXR (22(R)-cholesterol or TO901317) or vehicle twice daily for 3 days. All activators significantly increased epidermal cholesterol, fatty acid, and sphingolipid synthesis, including the production of barrier-specific ceramide species. In addition, lamellar body (LB) formation, secretion, and post-secretory processing accelerated significantly following acute barrier disruption in PPAR/LXR-activator-treated animals. Finally, the activity of epidermal β-glucocerebrosidase, a key lipid-processing enzyme, increased in PPAR/LXR-activator-treated animals. Thus, topical PPAR and LXR activators stimulate epidermal lipid synthesis, increase LB secretion, and accelerate extracellular lipid processing, providing additional mechanisms that further account for their ability to improve epidermal permeability barrier homeostasis. Since the liposensors are activated by endogenous lipid metabolites, they may serve as unique regulators of barrier homeostasis.

Original languageEnglish
Pages (from-to)386-392
Number of pages7
JournalJournal of Investigative Dermatology
Volume126
Issue number2
DOIs
Publication statusPublished - 2006 Feb 1

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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