title: Vascular endothelial growth factor stimulates embryonic urinary bladder development in organ culture.
abstract: OBJECTIVE
  To determine whether vascular endothelial growth factor A (VEGF) and its receptors are expressed during bladder development in mice when capillaries are forming, and whether exogenous VEGF might enhance the growth of endothelia and other types of bladder cells, using an embryonic organ-culture model.
  
  
  METHODS
  Whole bladders from wild-type mice, at embryonic day (E) 14, were grown in serum-free organ culture in an air/5% CO2 atmosphere; some cultures were supplemented with VEGF and/or with VEGF receptor 1/Fc chimera (VEGFR1/Fc), which blocks VEGF bioactivity. Organs were harvested after 6 days and the expression of VEGF and related molecules assessed using immunohistochemistry.
  
  
  RESULTS
  VEGF, VEGFR1 and VEGFR2 positive cells were immunodetected in E14 and E18 bladders. Exogenous VEGF increased whole-organ growth, as assessed by explant areas, total cell numbers, DNA and protein content; proliferation was enhanced, and apoptosis decreased, in urothelium and surrounding tissues. VEGF also increased the proportions of cells expressing endothelial (CD31) and smooth muscle (alpha smooth muscle actin) markers. VEGFR1/Fc blocked the growth-enhancing effects of exogenous VEGF.
  
  
  CONCLUSIONS
  In organ culture, exogenous VEGF not only stimulated embryonic bladder endothelial cells but also strikingly enhanced the growth of the whole organ. Whether the effects of VEGF on diverse bladder cell populations are direct or indirect requires further investigation. The finding that VEGF protein is present in embryonic bladders in vivo raises the possibility that it has similar actions during normal development. The results also illuminate the pathobiology of certain bladder diseases in which VEGF levels have been shown to be increased.
authors.affiliation: Nephro-Urology Unit, Institute of Child Health, University College London, London, UK. berkburgu@hotmail.com
authors.forename: Berk
authors.initials: B
authors.lastname: Burgu
authors.forename: Liam S
authors.initials: LS
authors.lastname: McCarthy
authors.forename: Vanita
authors.initials: V
authors.lastname: Shah
authors.forename: David A
authors.initials: DA
authors.lastname: Long
authors.forename: Duncan T
authors.initials: DT
authors.lastname: Wilcox
authors.forename: Adrian S
authors.initials: AS
authors.lastname: Woolf
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005434:Flow Cytometry; D007150:Immunohistochemistry; D051379:Mice; D009130:Muscle, Smooth / Q000196:embryology; D001743:Urinary Bladder / Q000196:embryology* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors