Protease-activated receptor 2 protects against VEGF inhibitor-induced glomerular endothelial and podocyte injury

Scientific Reports
Yuji OeNobuyuki Takahashi

Abstract

Vascular endothelial growth factor (VEGF) inhibitors cause glomerular injury. We have recently shown that activation of protease-activated receptor 2 (PAR2) by factor Xa exacerbated diabetic kidney disease. However, the role of PAR2 in glomerular injury induced by VEGF blockade is not known. Herein, we investigated the effect of the lack of PAR2 on VEGF inhibitor-induced glomerular injury. Although administering an anti-VEGF antibody by itself did not show renal phenotype in wild type mice, its administration to mice lacking endothelial nitric oxide synthase (eNOS) caused glomerular injury. Different from what we expected, administration of an anti-VEGF antibody in mice lacking PAR2 and eNOS exacerbated albuminuria and reduced the expression levels of CD31, pro-angiogenic VEGF, and angiogenesis-related chemokines in their kidneys. Podocyte injury was also evident in this model of mice lacking PAR2. Our results suggest that PAR2 is protective against VEGF inhibitor-induced glomerular endothelial and podocyte injury.

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Citations

Mar 24, 2020·American Journal of Physiology. Renal Physiology·Shohei MitsuiNobuyuki Takahashi
Oct 31, 2020·Clinical and Experimental Pharmacology & Physiology·Kana Maruyama-FumotoSatomi Kagota

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Methods Mentioned

BETA
electron microscopy
ELISA
PCR

Software Mentioned

JMP
ImageJ
Image J

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