Vascular endothelial cadherin modulates renal interstitial fibrosis

Ikuyo Yamaguchi, Bie Nga Tchao, Megan L. Burger, Muneharu Yamada, Toshitake Hyodo, Costanza Giampietro, Allison A. Eddy

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)e20-e31
JournalNephron - Experimental Nephrology
Volume120
Issue number1
DOIs
StatePublished - Mar 2012
Externally publishedYes

Keywords

  • Renal fibrosis
  • Renal microcirculation
  • Unilateral ureteral obstruction
  • Vascular endothelial cadherin

ASJC Scopus subject areas

  • Physiology
  • Genetics
  • Nephrology

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