title: BAMBI regulates angiogenesis and endothelial homeostasis through modulation of alternative TGFβ signaling.
abstract: BACKGROUND
  BAMBI is a type I TGFβ receptor antagonist, whose in vivo function remains unclear, as BAMBI(-/-) mice lack an obvious phenotype.
  
  
  RESULTS
  Identifying BAMBI's functions requires identification of cell-specific expression of BAMBI. By immunohistology we found BAMBI expression restricted to endothelial cells and by electron microscopy BAMBI(-/-) mice showed prominent and swollen endothelial cells in myocardial and glomerular capillaries. In endothelial cells over-expression of BAMBI reduced, whereas knock-down enhanced capillary growth and migration in response to TGFβ. In vivo angiogenesis was enhanced in matrigel implants and in glomerular hypertrophy after unilateral nephrectomy in BAMBI(-/-) compared to BAMBI(+/+) mice consistent with an endothelial phenotype for BAMBI(-/-) mice. BAMBI's mechanism of action in endothelial cells was examined by canonical and alternative TGFβ signaling in HUVEC with over-expression or knock-down of BAMBI. BAMBI knockdown enhanced basal and TGFβ stimulated SMAD1/5 and ERK1/2 phosphorylation, while over-expression prevented both.
  
  
  CONCLUSIONS
  Thus we provide a first description of a vascular phenotype for BAMBI(-/-) mice, and provide in vitro and in vivo evidence that BAMBI contributes to endothelial and vascular homeostasis. Further, we demonstrate that in endothelial cells BAMBI interferes with alternative TGFβ signaling, most likely through the ALK 1 receptor, which may explain the phenotype observed in BAMBI(-/-) mice. This newly described role for BAMBI in regulating endothelial function has potential implications for understanding and treating vascular disease and tumor neo-angiogenesis.
authors: Department of Medicine, Mount Sinai School of Medicine, New York, New York, United States of America.
authors: Nicolas
authors: N
authors: Guillot
authors: Dmitrij
authors: D
authors: Kollins
authors: Victoria
authors: V
authors: Gilbert
authors: Sandhya
authors: S
authors: Xavier
authors: Jun
authors: J
authors: Chen
authors: Madeleine
authors: M
authors: Gentle
authors: Anand
authors: A
authors: Reddy
authors: Erwin
authors: E
authors: Bottinger
authors: Rulang
authors: R
authors: Jiang
authors: Maria Pia
authors: MP
authors: Rastaldi
authors: Alessandro
authors: A
authors: Corbelli
authors: Detlef
authors: D
authors: Schlondorff
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic / Q000502:physiology*; D009392:Nephrectomy; D010766:Phosphorylation; D015398:Signal Transduction / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: C485672:Bambi protein, mouse; D008565:Membrane Proteins; D016212:Transforming Growth Factor beta