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

T Shindo, I Manabe, Y Fukushima, K Tobe, K Aizawa… - Nature medicine, 2002 - nature.com
T Shindo, I Manabe, Y Fukushima, K Tobe, K Aizawa, S Miyamoto, K Kawai-Kowase…
Nature medicine, 2002nature.com
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 …
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-β (TGF-β) 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.
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