The Forkhead Box M1 Transcription Factor Is Essential for Embryonic Development of Pulmonary Vasculature

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