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-β (PPARβ-also referred to as PPARδ) are just beginning to emerge. It has recently become clear that PPARβ has a function in epithelial tissues, but controversy exists due to inconsistencies in the literature. There is strong evidence that ligand activation of PPARβ can induce terminal differentiation of keratinocytes, with a concomitant inhibition of cell proliferation. However, the role of PPARβ in keratinocyte-specific apoptosis is less clear. Additionally, the role of PPARβ in colonic epithelium remains unclear due to conflicting evidence suggesting that ligand activation of PPARβ can potentiate, as well as attenuate, intestinal cancer. Recent studies revealed that ligand activation of PPARβ 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 PPARβ for treating obesity, dyslipidemias and type 2 diabetes. Therefore, it becomes critical to determine the safety of PPARβ ligands. This review focuses on recent literature describing the role of PPARβ in epithelial tissues and highlights critical discrepancies that need to be resolved for a more comprehensive understanding of how this receptor modulates epithelial homeostasis.