title: Vascular endothelial cadherin modulates renal interstitial fibrosis.
abstract: OBJECTIVE
  Renal interstitial fibrosis is a final common pathway of all chronic, progressive kidney diseases. Peritubular capillary rarefaction is strongly correlated with fibrosis. The adherens junction protein vascular endothelial cadherin (VE-cadherin) is thought to play a critical role in vascular integrity. We hypothesized that VE-cadherin modulates the renal microcirculation during fibrogenesis and ultimately affects renal fibrosis.
  
  
  METHODS
  Unilateral ureteral obstruction (UUO) was used as a renal fibrosis model in VE-cadherin heterozygote (VE+/-) and wild-type (WT) mice, and the kidneys were harvested at days 3, 7, and 14. Peritubular capillary changes and fibrogenesis were investigated.
  
  
  RESULTS
  VE+/- mice had lower levels of VE-cadherin protein than WT mice at 3 and 7, but not 14 days after UUO. Vascular permeability was significantly greater in VE+/- mice 7 days after UUO, while peritubular capillary density was not significantly different in VE+/- and WT mice. Interstitial myofibroblast numbers and collagen I and III mRNA levels were significantly higher in VE+/- mice, consistent with a stronger early fibrogenic response. Expression of the pericyte marker neuron-glial antigen 2 was upregulated after UUO, but was not greater in VE+/- mice compared to the WT mice.
  
  
  CONCLUSIONS
  Our data suggest that VE-cadherin controls vascular permeability and limits fibrogenesis after UUO.
authors: Department of Pediatrics, University of Washington, Seattle, WA 98101-1309, USA. ikuyo.yamaguchi@seattlechildrens.org
authors: Ikuyo
authors: I
authors: Yamaguchi
authors: Bie Nga
authors: BN
authors: Tchao
authors: Megan L
authors: ML
authors: Burger
authors: Muneharu
authors: M
authors: Yamada
authors: Toshitake
authors: T
authors: Hyodo
authors: Costanza
authors: C
authors: Giampietro
authors: Allison A
authors: AA
authors: Eddy
mesh_terms: D000818:Animals; D000941:Antigens / Q000235:genetics / Q000378:metabolism; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002199:Capillary Permeability / Q000235:genetics / Q000502:physiology; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D005355:Fibrosis; D015870:Gene Expression; D006579:Heterozygote; D007150:Immunohistochemistry; D007668:Kidney / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D058628:Myofibroblasts / Q000378:metabolism / Q000473:pathology; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D012079:Renal Circulation / Q000235:genetics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014517:Ureteral Obstruction / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D000099216:Chondroitin Sulfate Proteoglycan 4; D000099152:Cadherin 5; D000097382:CD68 Molecule
chemical_list: D000941:Antigens; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015820:Cadherins; D024042:Collagen Type I; D024061:Collagen Type III; D005353:Fibronectins; D011509:Proteoglycans; D000099216:Chondroitin Sulfate Proteoglycan 4; D000099152:Cadherin 5; C067980:CD68 antigen, human; D000097382:CD68 Molecule