Contributions of peroxisome proliferator-activated receptor β/δ to skin health and disease

Abstract

Among the three peroxisome proliferatoractivated receptor (PPAR) transcription factors, PPAR β/δ is the isotype with the broadest expression pattern. In fact, the expression of PPAR β/δ is ubiquitous, albeit at levels that are tightly regulated. Herein, we reviewed its multiple functions in skin health and disease. PPAR β/δ has pro-differentiating effects in keratinocytes, regulates sebocyte differentiation, and promotes hair follicle growth in healthy skin. Furthermore, we reviewed novel insights into the roles of PPAR β/δ in skin wound healing, especially in inhibiting apoptosis and in modulating keratinocyte proliferation and migration. Therefore, PPAR β/δ represents a research target for the understanding and treatment of inflammatory skin diseases, such as psoriasis and acne vulgaris. In addition, PPAR β/δ is a tumor growth modifier. Epidemiological studies have established that tumor progression may be exacerbated by chronic low-grade inflammation, a condition promoting the production of the lipids that act as modulators of PPAR β/δ activity. The action of PPAR β/δ in skin cancer is ambivalent, which might be explained by this receptor ' s putative highly context-specific behavior, which depends on a combination of factors ranging from receptor expression levels to co-regulator distribution, diversity and activity of the ligands produced, and other tissue-specific conditions. Given its diverse and crucial roles in many tissues and organs, PPAR β/δ will remain a major focus of future research.