Center for Integrative Genomics, National Research Center "Frontiers in Genetics", University of Lausanne, Genopode Building, CH-1015 Lausanne, Switzerland.
Prostaglandins Leukot Essent Fatty Acids. 2011 Nov;85(5):235-43. doi: 10.1016/j.plefa.2011.04.016. Epub 2011 Jul 20.
Peroxisome proliferator-activated receptors (PPARs) are fatty acid-activated transcription factors belonging to the nuclear hormone receptor family. While PPARs are best known as regulators of energy homeostasis, evidence also has accumulated recently for their involvement in basic cellular functions. We review novel insights into PPAR functions in skin wound healing and liver, with emphasis on PPARβ/δ and PPARα, respectively. Activation of PPARβ/δ expression in response to injury promotes keratinocyte survival, directional sensing, and migration over the wound bed. In addition, interleukin (IL)-1 produced by the keratinocytes activates PPARβ/δ expression in the underlying fibroblasts, which hinders the mitotic activity of keratinocytes via inhibition of IL-1 signaling. Initially, roles were identified for PPARα in fatty acid catabolism. However, PPARα is also involved in downregulating many genes in female mammals. We have elucidated the mechanism of this repression, which requires sumoylation of PPARα. Physiologically, this control confers protection against estrogen-induced intrahepatic cholestasis.
过氧化物酶体增殖物激活受体 (PPARs) 是脂肪酸激活的转录因子，属于核激素受体家族。虽然 PPARs 作为能量稳态的调节剂而广为人知，但最近也有证据表明它们参与了基本的细胞功能。我们综述了 PPAR 在皮肤创伤愈合和肝脏中的新功能，分别强调了 PPARβ/δ 和 PPARα。损伤后 PPARβ/δ 的表达激活促进角质细胞的存活、定向感应和在创面床的迁移。此外，角质细胞产生的白细胞介素 (IL)-1 激活下方成纤维细胞中的 PPARβ/δ 表达，通过抑制 IL-1 信号来抑制角质细胞的有丝分裂活性。最初，PPARα 的作用被确定为脂肪酸代谢。然而，PPARα 也参与下调雌性哺乳动物的许多基因。我们阐明了这种抑制的机制，这需要 PPARα 的 SUMOylation。从生理上讲，这种控制赋予了对雌激素诱导的肝内胆汁淤积的保护作用。
