Kruppel-like zinc-finger transcription factor KLF5/BTEB2 is a target for angiotensin II signaling and an essential regulator of cardiovascular remodeling

被引：336

作者：

Shindo, T

Manabe, I

Fukushima, Y

Tobe, K

Aizawa, K

Miyamoto, S

Kowase, KK

Moriyama, N

Imai, Y

Kawakami, H

Nishimatsu, H

Ishikawa, T

Suzuki, T

Morita, H

Maemura, K

Sata, M

Hirata, Y

Komukai, M

Kagechika, H

Kadowaki, T

Kurabayashi, M

Nagai, R ^{[1
]}

机构：

[1] Univ Tokyo, Grad Sch Med, Dept Cardiovasc Med, Tokyo, Japan

[2] Univ Tokyo, Grad Sch Med, Dept Gastroenterol, Tokyo, Japan

[3] Univ Tokyo, Grad Sch Med, Dept Metab Dis, Tokyo, Japan

[4] Univ Tokyo, Grad Sch Med, Dept Urol, Tokyo, Japan

[5] Univ Tokyo, Grad Sch Pharmaceut Sci, Tokyo, Japan

[6] Gunma Univ, Sch Med, Dept Internal Med 2, Gunma, Japan

[7] Kyorin Univ, Dept Anat, Tokyo, Japan

[8] Inst Med Mol Design Inc, Tokyo, Japan

来源：

NATURE MEDICINE | 2002年 / 8卷 / 08期

关键词：

D O I：

10.1038/nm738

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We recently isolated a Kruppel-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.

引用

页码：856 / 863

页数：8

共 33 条

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