Krüppel-like zinc-finger transcription factor KLF5/BTEB2 is a target for angiotensin II signaling and an essential regulator of cardiovascular remodeling.
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.
Shindo
Takayuki
T
Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Manabe
Ichiro
I
Fukushima
Yasushi
Y
Tobe
Kazuyuki
K
Aizawa
Kenichi
K
Miyamoto
Saku
S
Kawai-Kowase
Keiko
K
Moriyama
Nobuo
N
Imai
Yasushi
Y
Kawakami
Hayato
H
Nishimatsu
Hiroaki
H
Ishikawa
Takashi
T
Suzuki
Toru
T
Morita
Hiroyuki
H
Maemura
Koji
K
Sata
Masataka
M
Hirata
Yasunobu
Y
Komukai
Masayuki
M
Kagechika
Hiroyuki
H
Kadowaki
Takashi
T
Kurabayashi
Masahiko
M
Nagai
Ryozo
R
D000804:Angiotensin II / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001808:Blood Vessels / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D024141:Collagen Type IV / Q000378:metabolism; D003984:Dibenzazepines / Q000494:pharmacology; D004064:Digestive System / Q000033:anatomy & histology; D004068:Digestive System Physiological Phenomena; D005260:Female; D017930:Genes, Reporter; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D009368:Neoplasm Transplantation; D018919:Neovascularization, Physiologic; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012176:Retinoids / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D020257:Ventricular Remodeling / Q000502:physiology*; D016335:Zinc Fingers
D024141:Collagen Type IV; D003984:Dibenzazepines; C492214:KLF5 protein, human; C118391:Klf5 protein, mouse; C492215:Klf5 protein, rat; D051741:Kruppel-Like Transcription Factors; C104182:LE 135; D010982:Platelet-Derived Growth Factor; D011993:Recombinant Fusion Proteins; D012176:Retinoids; D015534:Trans-Activators; C075278:platelet-derived growth factor A; D000804:Angiotensin II