Center for Theoretical Problems in Physico-Chemical Pharmacology, Russian Academy of Sciences, Moscow 109029, Russia.
NF Filatov Clinical Institute of Children's Health at I.M. Sechenov First MSMU, Moscow 119435, Russia.
Int J Mol Sci. 2022 Aug 26;23(17):9708. doi: 10.3390/ijms23179708.
The peroxisome proliferator-activated receptor PPAR-γ is one of three PPAR nuclear receptors that act as ligand-activated transcription factors. In immune cells, the skin, and other organs, PPAR-γ regulates lipid, glucose, and amino acid metabolism. The receptor translates nutritional, pharmacological, and metabolic stimuli into the changes in gene expression. The activation of PPAR-γ promotes cell differentiation, reduces the proliferation rate, and modulates the immune response. In the skin, PPARs also contribute to the functioning of the skin barrier. Since we know that the route from identification to the registration of drugs is long and expensive, PPAR-γ agonists already approved for other diseases may also represent a high interest for psoriasis. In this review, we discuss the role of PPAR-γ in the activation, differentiation, and proliferation of skin and immune cells affected by psoriasis and in contributing to the pathogenesis of the disease. We also evaluate whether the agonists of PPAR-γ may become one of the therapeutic options to suppress the inflammatory response in lesional psoriatic skin and decrease the influence of comorbidities associated with psoriasis.
过氧化物酶体增殖物激活受体 PPAR-γ 是三种 PPAR 核受体之一，作为配体激活转录因子发挥作用。在免疫细胞、皮肤和其他器官中，PPAR-γ 调节脂质、葡萄糖和氨基酸代谢。该受体将营养、药理学和代谢刺激转化为基因表达的变化。PPAR-γ 的激活促进细胞分化、降低增殖率并调节免疫反应。在皮肤中，PPARs 也有助于皮肤屏障的功能。由于我们知道从鉴定到药物注册的途径漫长且昂贵，因此已经批准用于其他疾病的 PPAR-γ 激动剂也可能对银屑病具有很高的兴趣。在这篇综述中，我们讨论了 PPAR-γ 在受银屑病影响的皮肤和免疫细胞的激活、分化和增殖中的作用，并探讨其在疾病发病机制中的作用。我们还评估了 PPAR-γ 的激动剂是否可能成为抑制病变性银屑病皮肤炎症反应和降低与银屑病相关的合并症影响的治疗选择之一。
