Vascular endothelial cadherin modulates renal interstitial fibrosis.

Yamaguchi I, Tchao BN, Burger ML, Yamada M, Hyodo T, Giampietro C, Eddy AA
Nephron Exp Nephrol. 2012 120 (1): e20-31

PMID: 22126970 · PMCID: PMC3254033 · DOI:10.1159/000332026

BACKGROUND/AIMS - 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.

CONCLUSION - Our data suggest that VE-cadherin controls vascular permeability and limits fibrogenesis after UUO.

Copyright © 2011 S. Karger AG, Basel.

MeSH Terms (25)

Animals Antigens Antigens, CD Antigens, Differentiation, Myelomonocytic Blotting, Western Cadherins Capillary Permeability Collagen Type I Collagen Type III Disease Models, Animal Fibronectins Fibrosis Gene Expression Heterozygote Immunohistochemistry Kidney Macrophages Mice Mice, Knockout Myofibroblasts Proteoglycans Renal Circulation Reverse Transcriptase Polymerase Chain Reaction Time Factors Ureteral Obstruction

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