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

Connections (1)

This publication is referenced by other Labnodes entities:

Links