Endothelial cell–restricted disruption of FoxM1 impairs endothelial repair following LPS-induced vascular injury

Zhao, Yan; Gao, Xiaopei; Zhao, Yidan; Mirza, M. B.; Frey, Randall S.; Kalinichenko, Vladimir V.; Wang, I‐Ching; Costa, Robert H.; Malik, Asrar B.

doi:10.1172/jci27154

Cited by 155 publications

(247 citation statements)

References 38 publications

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“…Therefore, increased tumor formation in Rosa26-Foxm1 transgenic mice can be explained by direct Foxm1 effect on proliferation of epithelial-derived tumor cells, or by effects of Foxm1 on tumor angiogenesis. This is consistent with previous reports demonstrating that Foxm1-depletion by siRNA transfection inhibits proliferation of both human adenocarcinoma A549 cells (Kim et al, 2006) and human microvascular endothelial HMEC-1 cells (Zhao et al, 2006). However, we were unable to detect significant differences in either the morphological appearance of pulmonary endothelial cells or the expression levels of endothelial-specific Pecam-1 protein in WT and Rosa26-Foxm1 lungs.…”

Section: Foxm1 Induces Formation Of Lung Tumors I-c Wang Et Alsupporting

confidence: 93%

“…Foxm1 expression transiently increases during acute lung injury and remains elevated until lung repair is completed (Kalinichenko et al, 2001b;Zhao et al, 2006). However, no significant differences in acute pulmonary inflammation were reported in previous studies for either BHT-treated Rosa26-Foxm1 mice (Kalinichenko et al, 2003) or LPS-treated Tie2-Cre Foxm1 fl/fl mice (Zhao et al, 2006).…”

Section: Foxm1 Induces Formation Of Lung Tumors I-c Wang Et Almentioning

confidence: 88%

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Transgenic expression of the forkhead box M1 transcription factor induces formation of lung tumors

et al. 2008

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The forkhead box m1 (Foxm1 or Foxm1b) protein (previously called HFH-11B, Trident, Win or MPP2) is abundantly expressed in human non-small cell lung cancers where it transcriptionally induces expression of genes essential for proliferation of tumor cells. In this study, we used Rosa26-Foxm1 transgenic mice, in which the Rosa26 promoter drives ubiquitous expression of Foxm1 transgene, to identify new signaling pathways regulated by Foxm1. Lung tumors were induced in Rosa26-Foxm1 mice using the 3-methylcholanthrene (MCA)/butylated hydroxytoluene (BHT) lung tumor initiation/promotion protocol. Tumors from MCA/BHTtreated Rosa26-Foxm1 mice displayed a significant increase in the number, size and DNA replication compared to wild-type mice. Elevated tumor formation in Rosa26-Foxm1 transgenic lungs was associated with persistent pulmonary inflammation, macrophage infiltration and increased expression of cyclooxygenase-2 (Cox-2), Cdc25C phosphatase, cyclin E2, chemokine ligands CXCL5, CXCL1 and CCL3, cathepsins and matrix metalloprotease-12. Cell culture experiments with A549 human lung adenocarcinoma cells demonstrated that depletion of Foxm1 by either short interfering RNA transfection or treatment with Foxm1-inhibiting ARF 26-44 peptide significantly reduced Cox-2 expression. In co-transfection experiments, Foxm1 protein-induced Cox-2 promoter activity and directly bound to the À2566/ À2580 bp region of human Cox-2 promoter.

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Section: Foxm1 Induces Formation Of Lung Tumors I-c Wang Et Alsupporting

confidence: 93%

Section: Foxm1 Induces Formation Of Lung Tumors I-c Wang Et Almentioning

confidence: 88%

Transgenic expression of the forkhead box M1 transcription factor induces formation of lung tumors

et al. 2008

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“…Furthermore, endothelial-specific disruption of Foxm1 diminished proliferation of endothelial cells following LPCinduced vascular injury (Zhao et al, 2006). Since Foxm1 is expressed in both cardiomyocytes and cardiac endothelial cells in the developing heart ( Fig.…”

Section: Endothelial-specific Deletion Of Foxm1 Fl/fl Allele Does Notmentioning

confidence: 90%

“…Conditional knockout mice containing an endothelial-specific deletion of the Foxm1 LoxP allele were generated by breeding Foxm1 LoxP/LoxP (fl/fl) mice with transgenic Tie2-Cre C57BL/6 mice (Zhao et al, 2006). Although 20% of Tie2-Cre Foxm1 fl/fl embryos died in late gestation/postnatally, the majority of Tie2-Cre Foxm1 fl/fl mice survived through birth and were capable of mating (Zhao et al, 2006).…”

Section: Foxm1 ؊/؊ Micementioning

confidence: 99%

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Myocardium defects and ventricular hypoplasia in mice homozygous null for the Forkhead Box m1 transcription factor

Ramakrishna

Kim

Petrovič

et al. 2007

Developmental Dynamics

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The Forkhead Box m1 (Foxm1) transcription factor is expressed in cardiomyocytes and cardiac endothelial cells during heart development. In this study, we used a novel Foxm1 ؊/؊ mouse line to demonstrate that Foxm1-deletion causes ventricular hypoplasia and diminished DNA replication and mitosis in developing cardiomyocytes. Proliferation defects in Foxm1 ؊/؊ hearts were associated with a reduced expression of Cdk1-activator Cdc25B phosphatase and NFATc3 transcription factor, and with abnormal nuclear accumulation of the Cdk-inhibitor p21 Cip1 protein. Depletion of Foxm1 levels by siRNA caused altered expression of these genes in cultured HL-1 cardiomyocytes. Endothelial-specific deletion of the Foxm1 fl/fl allele in Tie2-Cre Foxm1 fl/fl embryos did not influence heart development and cardiomyocyte proliferation. Foxm1 protein binds to the ؊9,259/؊9,288-bp region of the endogenous mouse NFATc3 promoter, indicating that Foxm1 is a transcriptional activator of the NFATc3 gene. Foxm1 regulates expression of genes essential for the proliferation of cardiomyocytes during heart development.

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Transcription factors regulating vasculogenesis and angiogenesis

Payne

Neal

Val

2023

Developmental Dynamics

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Transcription factors (TFs) play a crucial role in regulating the dynamic and precise patterns of gene expression required for the initial specification of endothelial cells (ECs), and during endothelial growth and differentiation. While sharing many core features, ECs can be highly heterogeneous. Differential gene expression between ECs is essential to pattern the hierarchical vascular network into arteries, veins and capillaries, to drive angiogenic growth of new vessels, and to direct specialization in response to local signals. Unlike many other cell types, ECs have no single master regulator, instead relying on differing combinations of a necessarily limited repertoire of TFs to achieve tight spatial and temporal activation and repression of gene expression. Here, we will discuss the cohort of TFs known to be involved in directing gene expression during different stages of mammalian vasculogenesis and angiogenesis, with a primary focus on development.

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Endothelial cell–restricted disruption of FoxM1 impairs endothelial repair following LPS-induced vascular injury

Cited by 155 publications

References 38 publications

Transgenic expression of the forkhead box M1 transcription factor induces formation of lung tumors

Transgenic expression of the forkhead box M1 transcription factor induces formation of lung tumors

Myocardium defects and ventricular hypoplasia in mice homozygous null for the Forkhead Box m1 transcription factor

Transcription factors regulating vasculogenesis and angiogenesis

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