TY - JOUR
T1 - Vascular endothelial cadherin modulates renal interstitial fibrosis
AU - Yamaguchi, Ikuyo
AU - Tchao, Bie Nga
AU - Burger, Megan L.
AU - Yamada, Muneharu
AU - Hyodo, Toshitake
AU - Giampietro, Costanza
AU - Eddy, Allison A.
PY - 2012/3
Y1 - 2012/3
N2 - 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.
AB - 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.
KW - Renal fibrosis
KW - Renal microcirculation
KW - Unilateral ureteral obstruction
KW - Vascular endothelial cadherin
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U2 - 10.1159/000332026
DO - 10.1159/000332026
M3 - Article
C2 - 22126970
AN - SCOPUS:84859791006
SN - 0028-2766
VL - 120
SP - e20-e31
JO - Nephron - Experimental Nephrology
JF - Nephron - Experimental Nephrology
IS - 1
ER -