Defects in Pulmonary Vasculature and Perinatal Lung Hemorrhage in Mice Heterozygous Null for the Forkhead Box f1 Transcription Factor

Kalinichenko, Vladimir V.; Lim, Lorena; Stolz, Donna B.; Shin, Brian; Rausa, Francisco M.; Clark, Jean C.; Whitsett, Jeffrey A.; Watkins, Simon C.; Costa, Robert H.

doi:10.1006/dbio.2001.0322

Cited by 174 publications

(247 citation statements)

References 62 publications

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“…Cell proliferation rates were detected by immunohistochemical staining of mouse lung paraffin sections using mouse monoclonal antibodies specific for BrdU (1:100; clone Bu 20A; Dako, Carpinteria, CA, USA) or PCNA (1:1000; clone PC-10; Roche Diagnostics, Indianapolis, IN, USA). Antibody-antigen complexes were detected by anti-mouse antibody conjugated with alkaline phosphatase and BCIP/NBT substrate (all from Vector Lab) as described (Kalinichenko et al, 2001aKim et al, 2005a). In each mouse lung, we counted the number of BrdU-positive cells per 1000 cells in ten distinct 400 Â microscope fields.…”

Section: Brdu Labeling and Immunohistochemical Stainingmentioning

confidence: 99%

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: Brdu Labeling and Immunohistochemical Stainingmentioning

confidence: 99%

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

et al. 2008

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“…Nuclear protein extracts were prepared from HL-1 cells, and then subjected to Western Blot analysis (Kalinichenko et al, 2001a) using mouse monoclonal antibody against cyclin B1 (1:500; GNS-11; BD Biosciences), p27 Kip1 (1:3,000; G173-524; BD Biosciences), or p21 Cip1 (1:200; SXM30; BD Biosciences). We also used rabbit polyclonal antibody against Cdk2 (1:1,500; M2; Santa Cruz) for loading controls.…”

Section: Western Blot Analysismentioning

confidence: 99%

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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“…Foxf1 and Foxf2 are expressed in lung mesenchyme. In addition, Foxf1 is abundant in subepithelial areas and in alveolar endothelial cells, where it regulates mesechyme-epithelial interactions, alveogenesis, and vascular remodelling (Hellqvist et al, 1996;Aitola et al, 2000;Costa et al, 2001;Kalinichenko et al, 2001;Mahlapuu et al, 2001;Lim et al, 2002;Ramirez et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Alterations in alveolar epithelium differentiation and vasculogenesis in lungs of LIF/IGF‐I double deficient embryos

Moreno-Barriuso¹,

López-Malpartida²,

Pablo³

et al. 2006

Developmental Dynamics

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Previous studies on double deficient mice for leukemia inhibitory factor (LIF) and insulin-like growth factor I (IGF-I) reported that they died of respiratory failure, with abnormal lung histology and altered expression of pulmonary markers. Here we analyzed prenatal Lif/Igf-I double mutant mouse embryos to characterize LIF and IGF-I cooperative roles in distal lung epithelium and vascular maturation. Lungs of IGF-I-deficient embryos displayed a higher proportion of type II pneumocytes, less differentiated type I pneumocytes, and failure in alveolar capillary remodeling compared to wild type and LIF-deficient mice. Lif/Igf-I double knockout lungs showed aggravated pulmonary hypoplasia, lower airway volume, increased proliferation, and elevated levels of ERK1/2 activation. In addition, their alveoli were collapsed and lined by type II cells. The differentiation of type I cells barely occurred and capillaries remained in the abundant mesenchyme. These results indicate that LIF collaborates with IGF-I in lung alveolar epithelium and vascular maturation.

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Defects in Pulmonary Vasculature and Perinatal Lung Hemorrhage in Mice Heterozygous Null for the Forkhead Box f1 Transcription Factor

Cited by 174 publications

References 62 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

Alterations in alveolar epithelium differentiation and vasculogenesis in lungs of LIF/IGF‐I double deficient embryos

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