title: New insights into the role of PPARs.
abstract: 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.
authors.affiliation: Center for Integrative Genomics, National Research Center "Frontiers in Genetics", University of Lausanne, Genopode Building, CH-1015 Lausanne, Switzerland.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Montagner
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Rando
authors.forename: Gwendoline
authors.initials: G
authors.lastname: Degueurce
authors.forename: Nicolas
authors.initials: N
authors.lastname: Leuenberger
authors.forename: Liliane
authors.initials: L
authors.lastname: Michalik
authors.forename: Walter
authors.initials: W
authors.lastname: Wahli
mesh_terms: D000818:Animals; D002780:Cholestasis, Intrahepatic / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D004734:Energy Metabolism; D004967:Estrogens / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000378:metabolism*; D008297:Male; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism*; D012727:Sex Characteristics; D015398:Signal Transduction; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D014945:Wound Healing
chemical_list: D004967:Estrogens; D005227:Fatty Acids; D007375:Interleukin-1; D047492:Peroxisome Proliferator-Activated Receptors