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

Yuji Oe, Tomofumi Fushima, Emiko Sato, Akiyo Sekimoto, Kiyomi Kisu, Hiroshi Sato, Junichi Sugawara, Sadayoshi Ito, Nobuyuki Takahashi

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

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.

Original languageEnglish
Article number2986
JournalScientific reports
Volume9
Issue number1
DOIs
Publication statusPublished - 2019 Dec 1

ASJC Scopus subject areas

  • General

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