The Forkhead Box m1 transcription factor is essential for embryonic development of pulmonary vasculature

Il-man Kim, Sneha Ramakrishna, Galina A. Gusarova, Helena M. Yoder, Robert H. Costa, Vladimir V. Kalinichenko

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

Transgenic and gene knock-out studies demonstrated that the mouse Forkhead Box m1 (Foxm1 or Foxm1b) transcription factor (previously called HFH-11B, Trident, Win, or MPP2) is essential for hepatocyte entry into mitosis during liver development, regeneration, and liver cancer. Targeted deletion of Foxm1 gene in mice produces an embryonic lethal phenotype due to severe abnormalities in the development of liver and heart. In this study, we show for the first time that Foxm1-/- lungs exhibit severe hypertrophy of arteriolar smooth muscle cells and defects in the formation of peripheral pulmonary capillaries as evidenced by significant reduction in platelet endothelial cell adhesion molecule 1 staining of the distal lung. Consistent with these findings, significant reduction in proliferation of the embryonic Foxm1-/- lung mesenchyme was found, yet proliferation levels were normal in the Foxm1-deficient epithelial cells. Severe abnormalities of the lung vasculature in Foxm1-/- embryos were associated with diminished expression of the transforming growth factor β receptor II, a disintegrin and metalloprotease domain 17 (ADAM-17), vascular endothelial growth factor receptors, Polo-like kinase 1, Aurora B kinase, laminin α4 (Lama4), and the Forkhead Box f1 transcription factor. Cotransfection studies demonstrated that Foxm1 stimulates transcription of the Lama4 promoter, and this stimulation requires the Foxm1 binding sites located between -1174 and -1145 bp of the mouse Lama4 promoter. In summary, development of mouse lungs depends on the Foxm1 transcription factor, which regulates expression of genes essential for mesenchyme proliferation, extracellular matrix remodeling, and vasculogenesis.

Original languageEnglish (US)
Pages (from-to)22278-22286
Number of pages9
JournalJournal of Biological Chemistry
Volume280
Issue number23
DOIs
StatePublished - Jun 10 2005

Fingerprint

Forkhead Transcription Factors
Liver
Embryonic Development
Transcription Factors
Genes
Lung
Aurora Kinase B
CD31 Antigens
Disintegrins
Vascular Endothelial Growth Factor Receptor
Growth Factor Receptors
Transforming Growth Factors
Metalloproteases
Laminin
Mesoderm
Transcription
Muscle
Binding Sites
Cells
Defects

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Kim, I., Ramakrishna, S., Gusarova, G. A., Yoder, H. M., Costa, R. H., & Kalinichenko, V. V. (2005). The Forkhead Box m1 transcription factor is essential for embryonic development of pulmonary vasculature. Journal of Biological Chemistry, 280(23), 22278-22286. https://doi.org/10.1074/jbc.M500936200

The Forkhead Box m1 transcription factor is essential for embryonic development of pulmonary vasculature. / Kim, Il-man; Ramakrishna, Sneha; Gusarova, Galina A.; Yoder, Helena M.; Costa, Robert H.; Kalinichenko, Vladimir V.

In: Journal of Biological Chemistry, Vol. 280, No. 23, 10.06.2005, p. 22278-22286.

Research output: Contribution to journalArticle

Kim, I, Ramakrishna, S, Gusarova, GA, Yoder, HM, Costa, RH & Kalinichenko, VV 2005, 'The Forkhead Box m1 transcription factor is essential for embryonic development of pulmonary vasculature', Journal of Biological Chemistry, vol. 280, no. 23, pp. 22278-22286. https://doi.org/10.1074/jbc.M500936200
Kim, Il-man ; Ramakrishna, Sneha ; Gusarova, Galina A. ; Yoder, Helena M. ; Costa, Robert H. ; Kalinichenko, Vladimir V. / The Forkhead Box m1 transcription factor is essential for embryonic development of pulmonary vasculature. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 23. pp. 22278-22286.
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