Submitted on January 7, 2008
Revised on January 8, 2008
Accepted on January 8, 2008
Peroxisome proliferator-activated receptors (PPAR) and liver X receptors (LXR) in epidermal biology
Matthias Schmuth, Yan J. Jiang, Sandrine Dubrac, Peter M. Elias, and Kenneth R. Feingold
Dept. of Dermatology, University of California, San Francisco, San Francisco, California 94121
Corresponding Author: schmuthm{at}derm.ucsf.edu
The epidermis is a very active site of lipid metabolism and all PPAR and LXR isoforms are expressed in the epidermis. Activation of PPAR alpha, beta/delta, or gamma or LXRs stimulates keratinocyte differentiation. Additionally, activation of these receptors also improves permeability barrier homeostasis by a number of mechanisms including stimulating epidermal lipid synthesis, increasing lamellar body formation and secretion, and increasing the activity of enzymes required for the extracellular processing of lipids in the stratum corneum leading to the formation of lamellar membranes that mediate permeability barrier function. The stimulation of keratinocyte differentiation and permeability barrier formation also occurs during fetal development resulting in accelerated epidermal development. PPAR and LXR activation regulate keratinocyte proliferation and apoptosis and studies have shown that these receptors play a role in cutaneous carcinogenesis. Lastly, PPAR and LXR activation is anti-inflammatory reducing inflammation in animal models of allergic and irritant contact dermatitis. Because of their broad profile of beneficial effects on skin homeostasis, PPAR and LXR have great potential to serve as drug targets for common skin disease such as psoriasis, atopic dermatitis and skin cancer.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
