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