title: Krüppel-like zinc-finger transcription factor KLF5/BTEB2 is a target for angiotensin II signaling and an essential regulator of cardiovascular remodeling.
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.
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Shindo
authors.forename: Ichiro
authors.initials: I
authors.lastname: Manabe
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Fukushima
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Tobe
authors.forename: Kenichi
authors.initials: K
authors.lastname: Aizawa
authors.forename: Saku
authors.initials: S
authors.lastname: Miyamoto
authors.forename: Keiko
authors.initials: K
authors.lastname: Kawai-Kowase
authors.forename: Nobuo
authors.initials: N
authors.lastname: Moriyama
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Imai
authors.forename: Hayato
authors.initials: H
authors.lastname: Kawakami
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nishimatsu
authors.forename: Takashi
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Toru
authors.initials: T
authors.lastname: Suzuki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Morita
authors.forename: Koji
authors.initials: K
authors.lastname: Maemura
authors.forename: Masataka
authors.initials: M
authors.lastname: Sata
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Hirata
authors.forename: Masayuki
authors.initials: M
authors.lastname: Komukai
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kagechika
authors.forename: Takashi
authors.initials: T
authors.lastname: Kadowaki
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kurabayashi
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
mesh_terms: 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
chemical_list: 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