TY - JOUR
T1 - Krüppel-like zinc-finger transcription factor KLF5/BTEB2 is a target for angiotensin II signaling and an essential regulator of cardiovascular remodeling
AU - Shindo, Takayuki
AU - Manabe, Ichiro
AU - Fukushima, Yasushi
AU - Tobe, Kazuyuki
AU - Aizawa, Kenichi
AU - Miyamoto, Saku
AU - Kawai-Kowase, Keiko
AU - Moriyama, Nobuo
AU - Imai, Yasushi
AU - Kawakami, Hayato
AU - Nishimatsu, Hiroaki
AU - Ishikawa, Takashi
AU - Suzuki, Toru
AU - Morita, Hiroyuki
AU - Maemura, Koji
AU - Sata, Masataka
AU - Hirata, Yasunobu
AU - Komukai, Masayuki
AU - Kagechika, Hiroyuki
AU - Kadowaki, Takashi
AU - Kurabayashi, Masahiko
AU - Nagai, Ryozo
N1 - Funding Information:
Acknowledgments We thank T. Collins for the PDGF-A reporter constructs, CT. Teng for the human IKLF construct; SF. Yet for the GKLF construct; R. Urrutia for the TIEG construct; and H. Kumagaya for the S180 cell line. This study was supported in part by a Grant-in-Aid for Millennium Projects from the Ministry of Health, Labor and Welfare, Japan and a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan.
PY - 2002/8
Y1 - 2002/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0036347210&partnerID=8YFLogxK
U2 - 10.1038/nm738
DO - 10.1038/nm738
M3 - 学術論文
C2 - 12101409
AN - SCOPUS:0036347210
SN - 1078-8956
VL - 8
SP - 856
EP - 863
JO - Nature Medicine
JF - Nature Medicine
IS - 8
ER -