| Literature DB >> 12101409 |
Takayuki Shindo1, Ichiro Manabe, Yasushi Fukushima, Kazuyuki Tobe, Kenichi Aizawa, Saku Miyamoto, Keiko Kawai-Kowase, Nobuo Moriyama, Yasushi Imai, Hayato Kawakami, Hiroaki Nishimatsu, Takashi Ishikawa, Toru Suzuki, Hiroyuki Morita, Koji Maemura, Masataka Sata, Yasunobu Hirata, Masayuki Komukai, Hiroyuki Kagechika, Takashi Kadowaki, Masahiko Kurabayashi, Ryozo Nagai.
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.Entities:
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Year: 2002 PMID： 12101409 DOI： 10.1038/nm738
Source DB: PubMed Journal: Nat Med ISSN： 1078-8956 Impact factor: 53.440