Krüppel-like zinc-finger transcription factor KLF5/BTEB2 is a target for angiotensin II signaling and an essential regulator of cardiovascular remodeling

Nat Med. 2002 Aug;8(8):856-63. doi: 10.1038/nm738. Epub 2002 Jul 8.

Abstract

We recently isolated a Krüppel-like zinc-finger transcription factor 5 (KLF5; also known as BTEB2 and IKLF), which is markedly induced in activated vascular smooth-muscle cells and fibroblasts. Here we describe our analysis of the in vivo function of KLF5 using heterozygous KLF5-knockout mice (Klf5(+/-)). In response to external stress, Klf5(+/-) mice showed diminished levels of arterial-wall thickening, angiogenesis, cardiac hypertrophy and interstitial fibrosis. Also, angiotensin II induced expression of KLF5, which in turn activated platelet-derived growth factor-A (PDGF-A) and transforming growth factor-beta (TGF-beta) expression. In addition, we determined that KLF5 interacted with the retinoic-acid receptor (RAR), that synthetic RAR ligands modulated KLF5 transcriptional activity, and that in vivo administration of RAR ligands affected stress responses in the cardiovascular system in a KLF5-dependent manner. KLF5 thus seems to be a key element linking external stress and cardiovascular remodeling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / metabolism*
  • Angiotensin II / pharmacology
  • Animals
  • Blood Vessels / cytology
  • Blood Vessels / drug effects
  • Blood Vessels / metabolism
  • Cells, Cultured
  • Collagen Type IV / metabolism
  • Dibenzazepines / pharmacology
  • Digestive System / anatomy & histology
  • Digestive System Physiological Phenomena
  • Female
  • Genes, Reporter
  • Humans
  • Kruppel-Like Transcription Factors
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myocardium / cytology
  • Myocardium / metabolism
  • Neoplasm Transplantation
  • Neovascularization, Physiologic
  • Platelet-Derived Growth Factor / genetics
  • Platelet-Derived Growth Factor / metabolism
  • Rats
  • Recombinant Fusion Proteins / metabolism
  • Retinoids / antagonists & inhibitors
  • Signal Transduction / physiology*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Ventricular Remodeling / physiology*
  • Zinc Fingers

Substances

  • Collagen Type IV
  • Dibenzazepines
  • KLF5 protein, human
  • Klf5 protein, mouse
  • Klf5 protein, rat
  • Kruppel-Like Transcription Factors
  • LE 135
  • Platelet-Derived Growth Factor
  • Recombinant Fusion Proteins
  • Retinoids
  • Trans-Activators
  • platelet-derived growth factor A
  • Angiotensin II