title: Caffeic acid induces keratinocyte differentiation by activation of PPAR-α.
abstract: OBJECTIVE
  Peroxisome proliferator-activated receptors (PPAR)-α plays an important role in epidermal differentiation and barrier recovery, and topical treatment with PPAR-α agonists restores epidermal homeostasis in essential fatty acid deficiency and permeability barrier in skin disruptions. Therefore, we performed structure-based pharmacophore screening to search for a novel PPAR-α agonist. Caffeic acid was ultimately selected and evaluated for its effects on keratinocyte differentiation and epidermal permeability barrier.
  
  
  METHODS
  The transactivation activity of PPAR-responsive element (PPRE) and cornified envelope (CE) formation were assayed. Also, immunoblot analysis and anti-oxidant activity were investigated on caffeic acid.
  
  
  RESULTS
  Caffeic acid increases the transactivation activity of PPRE and CE formation in keratinocytes. In addition, caffeic acid promotes the expression of genes and proteins related to CE formation such as involucrin and transglutaminase-1. Additionally, anti-oxidant activity were improved by caffeic acid.
  
  
  CONCLUSIONS
  Caffeic acid can promote keratinocyte differentiation and restore skin barrier homeostasis and is suggested to be an appropriate skin therapeutic agent for improving epidermal permeability barrier function.
authors.affiliation: R&D Center of Skin Science and Cosmetics, Enprani Co., Ltd, Incheon, Korea.
authors.forename: Bora
authors.initials: B
authors.lastname: Kim
authors.forename: Jin Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Hyun-Soo
authors.initials: HS
authors.lastname: Kim
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D002109:Caffeic Acids / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D002460:Cell Line; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D010539:Permeability / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics; D011503:Transglutaminases / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; D002109:Caffeic Acids; D047495:PPAR gamma; D011503:Transglutaminases; C105804:transglutaminase 1; C040048:caffeic acid
keywords: caffeic acid; keratinocyte differentiation; peroxisome proliferator-activated receptors; structure-based pharmacophore screening