Krüppel-like zinc-finger transcription factor KLF5/BTEB2 is a target for angiotensin II signaling and an essential regulator of cardiovascular remodeling
Copyright policy )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(+/-)). 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.
- University of Tokyo Japan
- Kyorin University Japan
- Gunma University Japan
- Institute of Medicinal Molecular Design Japan
Collagen Type IV, Male, Mice, Knockout, Platelet-Derived Growth Factor, Angiotensin II, Myocardium, Kruppel-Like Transcription Factors, Neovascularization, Physiologic, Mice, Inbred C57BL, Mice, Dibenzazepines, Digestive System Physiological Phenomena, Genes, Reporter, Animals, Blood Vessels, Humans, Female, Digestive System, Cells, Cultured, Neoplasm Transplantation
Collagen Type IV, Male, Mice, Knockout, Platelet-Derived Growth Factor, Angiotensin II, Myocardium, Kruppel-Like Transcription Factors, Neovascularization, Physiologic, Mice, Inbred C57BL, Mice, Dibenzazepines, Digestive System Physiological Phenomena, Genes, Reporter, Animals, Blood Vessels, Humans, Female, Digestive System, Cells, Cultured, Neoplasm Transplantation
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