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

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(... Full description

Journal Title: Nature medicine 2002-08, Vol.8 (8), p.856-863
Main Author: Nagai, Ryozo
Other 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 , Kadowaki, Takashi , Kurabayashi, Masahiko
Format: Electronic Article Electronic Article
Language: English
Subjects:
Publisher: United States: Nature Publishing Group
ID: ISSN: 1078-8956
Link: https://www.ncbi.nlm.nih.gov/pubmed/12101409
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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
format: Article
creator:
  • Nagai, Ryozo
  • 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
subjects:
  • Analysis
  • Angiotensin
  • Angiotensin II - metabolism
  • Angiotensin II - pharmacology
  • Animals
  • Blood Vessels - cytology
  • Blood Vessels - drug effects
  • Blood Vessels - metabolism
  • Cells, Cultured
  • Collagen Type IV - metabolism
  • Dibenzazepines - pharmacology
  • Digestive System - anatomy & histology
  • Digestive System Physiological Phenomena
  • Female
  • Genes, Reporter
  • Humans
  • Kruppel-Like Transcription Factors
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myocardium - cytology
  • Myocardium - metabolism
  • Neoplasm Transplantation
  • Neovascularization, Physiologic
  • Platelet-Derived Growth Factor - genetics
  • Platelet-Derived Growth Factor - metabolism
  • Rats
  • Recombinant Fusion Proteins - metabolism
  • Research
  • Retinoids - antagonists & inhibitors
  • Signal Transduction - physiology
  • Trans-Activators - genetics
  • Trans-Activators - metabolism
  • Transcription factors
  • Ventricular Remodeling - physiology
  • Zinc Fingers
ispartof: Nature medicine, 2002-08, Vol.8 (8), p.856-863
description: 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.
language: eng
source:
identifier: ISSN: 1078-8956
fulltext: no_fulltext
issn:
  • 1078-8956
  • 1546-170X
url: Link


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titleKrüppel-like zinc-finger transcription factor KLF5/BTEB2 is a target for angiotensin II signaling and an essential regulator of cardiovascular remodeling
creatorNagai, Ryozo ; 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
creatorcontribNagai, Ryozo ; 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
descriptionWe 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.
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languageeng
publisherUnited States: Nature Publishing Group
subjectAnalysis ; Angiotensin ; Angiotensin II - metabolism ; Angiotensin II - pharmacology ; Animals ; Blood Vessels - cytology ; Blood Vessels - drug effects ; Blood Vessels - metabolism ; Cells, Cultured ; Collagen Type IV - metabolism ; Dibenzazepines - pharmacology ; Digestive System - anatomy & histology ; Digestive System Physiological Phenomena ; Female ; Genes, Reporter ; Humans ; Kruppel-Like Transcription Factors ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Myocardium - cytology ; Myocardium - metabolism ; Neoplasm Transplantation ; Neovascularization, Physiologic ; Platelet-Derived Growth Factor - genetics ; Platelet-Derived Growth Factor - metabolism ; Rats ; Recombinant Fusion Proteins - metabolism ; Research ; Retinoids - antagonists & inhibitors ; Signal Transduction - physiology ; Trans-Activators - genetics ; Trans-Activators - metabolism ; Transcription factors ; Ventricular Remodeling - physiology ; Zinc Fingers
ispartofNature medicine, 2002-08, Vol.8 (8), p.856-863
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0Nagai, Ryozo
1Shindo, Takayuki
2Manabe, Ichiro
3Fukushima, Yasushi
4Tobe, Kazuyuki
5Aizawa, Kenichi
6Miyamoto, Saku
7Kawai-Kowase, Keiko
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11Nishimatsu, Hiroaki
12Ishikawa, Takashi
13Suzuki, Toru
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16Sata, Masataka
17Hirata, Yasunobu
18Komukai, Masayuki
19Kagechika, Hiroyuki
20Kadowaki, Takashi
21Kurabayashi, Masahiko
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0Krüppel-like zinc-finger transcription factor KLF5/BTEB2 is a target for angiotensin II signaling and an essential regulator of cardiovascular remodeling
1Nature medicine
addtitleNat Med
descriptionWe 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.
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0Analysis
1Angiotensin
2Angiotensin II - metabolism
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4Animals
5Blood Vessels - cytology
6Blood Vessels - drug effects
7Blood Vessels - metabolism
8Cells, Cultured
9Collagen Type IV - metabolism
10Dibenzazepines - pharmacology
11Digestive System - anatomy & histology
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14Genes, Reporter
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27Rats
28Recombinant Fusion Proteins - metabolism
29Research
30Retinoids - antagonists & inhibitors
31Signal Transduction - physiology
32Trans-Activators - genetics
33Trans-Activators - metabolism
34Transcription factors
35Ventricular Remodeling - physiology
36Zinc Fingers
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16Sata, Masataka
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titleKrüppel-like zinc-finger transcription factor KLF5/BTEB2 is a target for angiotensin II signaling and an essential regulator of cardiovascular remodeling
authorNagai, Ryozo ; 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
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1Angiotensin
2Angiotensin II - metabolism
3Angiotensin II - pharmacology
4Animals
5Blood Vessels - cytology
6Blood Vessels - drug effects
7Blood Vessels - metabolism
8Cells, Cultured
9Collagen Type IV - metabolism
10Dibenzazepines - pharmacology
11Digestive System - anatomy & histology
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16Kruppel-Like Transcription Factors
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21Myocardium - cytology
22Myocardium - metabolism
23Neoplasm Transplantation
24Neovascularization, Physiologic
25Platelet-Derived Growth Factor - genetics
26Platelet-Derived Growth Factor - metabolism
27Rats
28Recombinant Fusion Proteins - metabolism
29Research
30Retinoids - antagonists & inhibitors
31Signal Transduction - physiology
32Trans-Activators - genetics
33Trans-Activators - metabolism
34Transcription factors
35Ventricular Remodeling - physiology
36Zinc Fingers
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1Shindo, Takayuki
2Manabe, Ichiro
3Fukushima, Yasushi
4Tobe, Kazuyuki
5Aizawa, Kenichi
6Miyamoto, Saku
7Kawai-Kowase, Keiko
8Moriyama, Nobuo
9Imai, Yasushi
10Kawakami, Hayato
11Nishimatsu, Hiroaki
12Ishikawa, Takashi
13Suzuki, Toru
14Morita, Hiroyuki
15Maemura, Koji
16Sata, Masataka
17Hirata, Yasunobu
18Komukai, Masayuki
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abstractWe 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.
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