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

Contributions of peroxisome proliferator-activated receptor β/δ to skin health and disease
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过氧化物酶体增殖物激活受体 β/δ 对皮肤健康和疾病的贡献

DOI:
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发表时间:
2013
影响因子:
--
通讯作者:
W. Wahli
W. Wahli
中科院分区:
--
文献类型:
--
作者:
A. Montagner;W. Wahli

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过氧化物酶体增殖物激活受体(peroxisome proliferator-activated receptor,PPAR)β/δ是三种转录因子中表达最广泛的一种。事实上,PPARβ/δ的表达是普遍存在的,尽管其水平受到严格调控。在此,我们综述了它在皮肤健康和疾病中的多种功能。PPARβ/δ在角质形成细胞中具有促分化作用,调节皮脂细胞分化,并促进健康皮肤中的毛囊生长。此外,我们回顾了新的见解,在皮肤伤口愈合中的作用,特别是在抑制细胞凋亡和调节角质形成细胞的增殖和迁移。因此,PPARβ/δ代表了了解和治疗炎症性皮肤病如银屑病和寻常痤疮的研究靶点。此外,PPARβ/δ是一种肿瘤生长调节剂。流行病学研究已经确定,慢性低度炎症可能会加剧肿瘤进展,慢性低度炎症是一种促进脂质产生的疾病,这些脂质可作为PPARβ/δ活性的调节剂。在皮肤癌中,PPARβ/δ的作用是矛盾的,这可以通过这种受体的假定的高度环境特异性行为来解释,其取决于从受体表达水平到共调节子分布、所产生的配体的多样性和活性以及其他组织特异性条件的因素的组合。鉴于其在许多组织和器官中的多样性和关键作用,PPARβ/δ仍将是未来研究的主要焦点。
Abstract Among the three peroxisome proliferator-activated receptor (PPAR) transcription factors, PPARβ/δ is the isotype with the broadest expression pattern. In fact, the expression of PPARβ/δ is ubiquitous, albeit at levels that are tightly regulated. Herein, we reviewed its multiple functions in skin health and disease. PPARβ/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 PPARβ/δ in skin wound healing, especially in inhibiting apoptosis and in modulating keratinocyte proliferation and migration. Therefore, PPARβ/δ represents a research target for the understanding and treatment of inflammatory skin diseases, such as psoriasis and acne vulgaris. In addition, PPARβ/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 PPARβ/δ activity. The action of PPARβ/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, PPARβ/δ will remain a major focus of future research.
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