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

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; Nagai, Ryozo

doi:10.1038/nm738

Cited by 350 publications

(356 citation statements)

References 33 publications

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“…In addition, microarray studies suggest that FGF-BP is a downstream gene of KLF5 in vitro and in vivo (Chen et al, 2006;Wan et al, 2008). Functionally, both genes promote cell transformation and angiogenesis (Czubayko et al, 1997;Shindo et al, 2002). Finally, both genes have been reported to be overexpressed in breast cancer (Kagan et al, 2003;Tong et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Krüppel-like factor 5 promotes breast cell proliferation partially through upregulating the transcription of fibroblast growth factor binding protein 1

et al. 2009

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The Kru¨ppel-like factor 5 (KLF5) is a zinc-finger transcription factor promoting cell proliferation, cellcycle progression and survival. A high expression level of KLF5 mRNA has been shown to be associated with shorter breast cancer patient survival. However, the mechanism of KLF5 action in breast cancer is still not clear. In this study, we found that both KLF5 and its downstream gene fibroblast growth factor binding protein 1 (FGF-BP) are co-expressed in breast cell lines and primary tumors. Manipulation of the KLF5 expression can positively regulate the FGF-BP mRNA and protein levels in multiple breast cell lines. In addition, the secreted FGF-BP protein in the conditional medium is also regulated by KLF5. Furthermore, we demonstrated that KLF5 binds and activates the FGF-BP promoter through a GC box by luciferase reporter, oligo pull down and chromatin immunoprecipitation (ChIP) assays. When FGF-BP is depleted by siRNA, KLF5 fails to promote cell proliferation in MCF10A, SW527 and TSU-Pr1. We further demonstrated that overexpression or addition of FGF-BP rescues the KLF5-knockdown-induced growth arrest in MCF10A cells. Finally, KLF5 significantly promotes MCF7 breast cancer cell xenograft growth in athymic nude mice. These findings suggest that KLF5 may promote breast cancer cell proliferation at least partially through directly activating the FGF-BP mRNA transcription. Understanding the mechanism of KLF5 action in breast cancer may result in useful diagnostic and therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

Krüppel-like factor 5 promotes breast cell proliferation partially through upregulating the transcription of fibroblast growth factor binding protein 1

et al. 2009

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“…KLF5 is normally markedly induced in activated vascular smooth muscle cells and fibroblasts. In response to external stress such as injury induced by a vascular cuff, Klf5 +/-mice showed diminished levels of arterial wall thickening, angiogenesis, cardiac hypertrophy and interstitial fibrosis [33]. This physiologic effect of KLF5 is in part mediated by its ability to activate expression of genes encoding platelet-derived growth factor-A (PDGF-A) and transforming growth factor-β (TGF-β) [33].…”

Section: Klf4 and Klf5 Exert Distinct Physiologic Functions In Vivo Amentioning

confidence: 99%

Krüppel-like factors 4 and 5: the yin and yang regulators of cellular proliferation

et al. 2005

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Krüppel-like factors (KLFs) are evolutionarily conserved zinc finger-containing transcription factors with diverse regulatory functions in cell growth, proliferation, differentiation, and embryogenesis. KLF4 and KLF5 are two closely related members of the KLF family that have a similar tissue distribution in embryos and adults. However, the two KLFs often exhibit opposite effects on regulation of gene transcription, despite binding to similar, if not identical, cis-acting DNA sequences. In addition, KLF4 and 5 exert contrasting effects on cell proliferation in many instances; while KLF4 is an inhibitor of cell growth, KLF5 stimulates proliferation. Here we review the biological properties and biochemical mechanisms of action of the two KLFs in the context of growth regulation.

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“…To date, there are four published reports describing the function of KLFs in the heart -KLF5 in cardiac fibroblasts [28], KLF15 (postnatal) [27] and KLF13 (embryonic) [37] in cardiomyocytes, and a brief report describing a cardiac phenotype in systemic KLF10-null mice [38]. Figure 1 highlights some of these published findings pertaining to KLFs in the myocardium.…”

Section: Klfs In the Heartmentioning

confidence: 99%

“…An appreciation for the importance of this factor in cardiac biology has been elegantly developed principally through studies in the laboratory of Dr. Ryozo Nagai [28]. As will be described later in this review, KLF5 has also been implicated as a central regulator of vascular smooth muscle cell differentiation, growth and gene expression.…”

Section: Klf5mentioning

confidence: 99%

Kruppel-like Factors (KLFs) in muscle biology

Haldar¹,

Ibrahim²,

Jain³

2007

Journal of Molecular and Cellular Cardiology

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The Kruppel-like Factor (KLF) family of zinc-finger transcription factors are critical regulators of cell differentiation, phenotypic modulation and physiologic function. An emerging body of evidence implicates an important role for these factors in cardiovascular biology, however, the role of KLFs in muscle biology is only beginning to be understood. This article reviews the published data describing the role of KLFs in cardiomyocytes, smooth muscle cells, and skeletal muscle and highlights the importance of these factors in cardiovascular development, physiology and disease pathobiology.

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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

Cited by 350 publications

References 33 publications

Krüppel-like factor 5 promotes breast cell proliferation partially through upregulating the transcription of fibroblast growth factor binding protein 1

Krüppel-like factor 5 promotes breast cell proliferation partially through upregulating the transcription of fibroblast growth factor binding protein 1

Krüppel-like factors 4 and 5: the yin and yang regulators of cellular proliferation

Kruppel-like Factors (KLFs) in muscle biology

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