Antiapoptotic role of PPARbeta in keratinocytes via transcriptional control of the Akt1 signaling pathway

Mol Cell. 2002 Oct;10(4):721-33. doi: 10.1016/s1097-2765(02)00646-9.

Abstract

Apoptosis, differentiation, and proliferation are cellular responses which play a pivotal role in wound healing. During this process PPARbeta translates inflammatory signals into prompt keratinocyte responses. We show herein that PPARbeta modulates Akt1 activation via transcriptional upregulation of ILK and PDK1, revealing a mechanism for the control of Akt1 signaling. The resulting higher Akt1 activity leads to increased keratinocyte survival following growth factor deprivation or anoikis. PPARbeta also potentiates NF-kappaB activity and MMP-9 production, which can regulate keratinocyte migration. Together, these results provide a molecular mechanism by which PPARbeta protects keratinocytes against apoptosis and may contribute to the process of skin wound closure.

MeSH terms

  • 3-Phosphoinositide-Dependent Protein Kinases
  • Animals
  • Anoikis / drug effects
  • Apoptosis* / drug effects
  • Blotting, Western
  • Cell Line
  • Electrophoretic Mobility Shift Assay
  • Gene Expression Regulation
  • Growth Substances / metabolism
  • Humans
  • Keratinocytes / cytology*
  • Keratinocytes / metabolism*
  • Matrix Metalloproteinase 9 / biosynthesis
  • Mice
  • NF-kappa B / metabolism
  • Protein-Serine-Threonine Kinases / biosynthesis
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt
  • Proto-Oncogene Proteins*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Signal Transduction*
  • Transcription Factors / metabolism*
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Growth Substances
  • NF-kappa B
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Receptors, Cytoplasmic and Nuclear
  • Transcription Factors
  • Tumor Necrosis Factor-alpha
  • integrin-linked kinase
  • 3-Phosphoinositide-Dependent Protein Kinases
  • AKT1 protein, human
  • PDPK1 protein, human
  • Pdpk1 protein, mouse
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Matrix Metalloproteinase 9