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, Kadowaki Takashi, Kurabayashi Masahiko, Nagai Ryozo
Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Nat Med. 2002 Aug;8(8):856-63. doi: 10.1038/nm738. Epub 2002 Jul 8.
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.
我们最近分离出一种类Krüppel锌指转录因子5（KLF5；也称为BTEB2和IKLF），其在活化的血管平滑肌细胞和成纤维细胞中显著诱导表达。在此，我们描述了使用杂合KLF5基因敲除小鼠（Klf5(+/-)）对KLF5体内功能的分析。在应对外部应激时，Klf5(+/-)小鼠的动脉壁增厚、血管生成、心脏肥大和间质纤维化水平降低。此外，血管紧张素II诱导KLF5表达，进而激活血小板衍生生长因子-A（PDGF-A）和转化生长因子-β（TGF-β）表达。此外，我们确定KLF5与视黄酸受体（RAR）相互作用，合成的RAR配体调节KLF5转录活性，并且在体内给予RAR配体以KLF5依赖的方式影响心血管系统的应激反应。因此，KLF5似乎是连接外部应激和心血管重塑的关键因素。
