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- Title
Krüppel-like zinc-finger transcription factor KLF5/BTEB2 is a target for angiotensin II signaling and an essential regulator of cardiovascular remodeling.
- Authors
Shindo, Takayuki; Manabe, Ichiro; Fukushima, Yasushi; Tobe, Kazuyuki; Aizawa, Kenichi; Miyamoto, Saku; Kawai-Kowase, Keiko; Moriyama, Nobuo; Imai, Yasushi; Kawakami, Hayato; Nishimatsu, Hiroaki; Ishikawa, Takashi; Suzuki, Toru; Morita, Hiroyuki; Maemura, Koji; Sata, Masataka; Hirata, Yasunobu; Komukai, Masayuki; Kagechika, Hiroyuki
- 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.
- Subjects
ANGIOTENSINS; RETINOIDS; CYTOKINES; TRANSCRIPTION factors
- Publication
Nature Medicine, 2002, Vol 8, Issue 8, p856
- ISSN
1078-8956
- Publication type
Article
- DOI
10.1038/nm738