Acyclic retinoid inhibits functional interaction of transcription factors Krüppel-like factor 5 and retinoic acid receptor-alpha

FEBS Lett. 2008 May 28;582(12):1755-60. doi: 10.1016/j.febslet.2008.04.040. Epub 2008 May 6.

Abstract

We show that transcription factor Krüppel-like factor 5 (KLF5), which is important in cardiovascular remodeling, interacts with retinoic acid receptor-alpha (RARalpha) to regulate downstream gene expression. Here, we investigated whether acyclic retinoid (ACR) regulates KLF5 and inhibits vascular remodeling. Co-immunoprecipitation and pull-down binding assay showed that ACR attenuates functional interaction of KLF5 and RARalpha. ACR affects KLF5 functions by regulating transactivation of platelet-derived growth factor A (PDGF-A) chain. ACR may be a new vascular therapy to target KLF5 in cardiovascular pathology.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Cattle
  • Cells, Cultured
  • Immunoprecipitation
  • Kruppel-Like Transcription Factors / antagonists & inhibitors*
  • Kruppel-Like Transcription Factors / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Physiologic / drug effects
  • Receptors, Retinoic Acid / antagonists & inhibitors*
  • Receptors, Retinoic Acid / metabolism
  • Retinoic Acid Receptor alpha
  • Transcription, Genetic / drug effects
  • Tretinoin / analogs & derivatives*
  • Tretinoin / pharmacology

Substances

  • Antineoplastic Agents
  • Klf5 protein, mouse
  • Kruppel-Like Transcription Factors
  • Rara protein, mouse
  • Receptors, Retinoic Acid
  • Retinoic Acid Receptor alpha
  • Tretinoin
  • 3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid