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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:
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
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
8Moriyama, Nobuo
9Imai, Yasushi
10Kawakami, Hayato
11Nishimatsu, Hiroaki
12Ishikawa, Takashi
13Suzuki, Toru
14Morita, Hiroyuki
15Maemura, Koji
16Sata, Masataka
17Hirata, Yasunobu
18Komukai, Masayuki
19Kagechika, Hiroyuki
20Kadowaki, Takashi
21Kurabayashi, Masahiko
title
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
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
12Digestive System Physiological Phenomena
13Female
14Genes, Reporter
15Humans
16Kruppel-Like Transcription Factors
17Male
18Mice
19Mice, Inbred C57BL
20Mice, Knockout
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22Myocardium - metabolism
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25Platelet-Derived Growth Factor - genetics
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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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14Morita, Hiroyuki
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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
12Digestive System Physiological Phenomena
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16Kruppel-Like Transcription Factors
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18Mice
19Mice, Inbred C57BL
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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
19Kagechika, Hiroyuki
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1Shindo, Takayuki
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7Kawai-Kowase, Keiko
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pages856-863
issn1078-8956
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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.
copUnited States
pubNature Publishing Group
pmid12101409
doi10.1038/nm738
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