The role of peroxisome proliferator-activated receptor-β/δ in epithelial cell growth and differentiation

The physiological and pharmacological roles of peroxisome proliferator-activated receptor-beta (PPAR beta-also referred to as PPAR delta) are just beginning to emerge. It has recently become clear that PPAR beta has a function in epithelial tissues, but controversy exists due to inconsistencies in the literature. There is strong evidence that ligand activation of PPAR can induce terminal differentiation of keratinocytes, with a concomitant inhibition of cell proliferation. However, the role of PPAR beta in keratinocyte-specific apoptosis is less clear. Additionally, the role of PPAR beta in colonic epithelium remains unclear due to conflicting evidence suggesting that ligand activation of PPAR beta can potentiate, as well as attenuate, intestinal cancer. Recent studies revealed that ligand activation of PPAR beta can induce fatty acid catabolism in skeletal muscle and is associated with improved insulin sensitivity, attenuated weight gain and elevated HDL levels thus demonstrating promising potential for targeting PPAR beta for treating obesity, dyslipidemias and type 2 diabetes. Therefore, it becomes critical to determine the safety of PPAR beta ligands. This review focuses on recent literature describing the role of PPAR beta in epithelial tissues and highlights critical discrepancies that need to be resolved for a more comprehensive understanding of how this receptor modulates epithelial homeostasis. (c) 2005 Elsevier Inc. All rights reserved.