Vascular Endothelial Cadherin Modulates Renal Interstitial Fibrosis

Abstract

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.