Cargando…
Protease-activated receptor 2 protects against VEGF inhibitor-induced glomerular endothelial and podocyte injury
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,...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6393426/ https://www.ncbi.nlm.nih.gov/pubmed/30814628 http://dx.doi.org/10.1038/s41598-019-39914-8 |
_version_ | 1783398687034048512 |
---|---|
author | Oe, Yuji Fushima, Tomofumi Sato, Emiko Sekimoto, Akiyo Kisu, Kiyomi Sato, Hiroshi Sugawara, Junichi Ito, Sadayoshi Takahashi, Nobuyuki |
author_facet | Oe, Yuji Fushima, Tomofumi Sato, Emiko Sekimoto, Akiyo Kisu, Kiyomi Sato, Hiroshi Sugawara, Junichi Ito, Sadayoshi Takahashi, Nobuyuki |
author_sort | Oe, Yuji |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6393426 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-63934262019-03-01 Protease-activated receptor 2 protects against VEGF inhibitor-induced glomerular endothelial and podocyte injury Oe, Yuji Fushima, Tomofumi Sato, Emiko Sekimoto, Akiyo Kisu, Kiyomi Sato, Hiroshi Sugawara, Junichi Ito, Sadayoshi Takahashi, Nobuyuki Sci Rep Article 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. Nature Publishing Group UK 2019-02-27 /pmc/articles/PMC6393426/ /pubmed/30814628 http://dx.doi.org/10.1038/s41598-019-39914-8 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Oe, Yuji Fushima, Tomofumi Sato, Emiko Sekimoto, Akiyo Kisu, Kiyomi Sato, Hiroshi Sugawara, Junichi Ito, Sadayoshi Takahashi, Nobuyuki Protease-activated receptor 2 protects against VEGF inhibitor-induced glomerular endothelial and podocyte injury |
title | Protease-activated receptor 2 protects against VEGF inhibitor-induced glomerular endothelial and podocyte injury |
title_full | Protease-activated receptor 2 protects against VEGF inhibitor-induced glomerular endothelial and podocyte injury |
title_fullStr | Protease-activated receptor 2 protects against VEGF inhibitor-induced glomerular endothelial and podocyte injury |
title_full_unstemmed | Protease-activated receptor 2 protects against VEGF inhibitor-induced glomerular endothelial and podocyte injury |
title_short | Protease-activated receptor 2 protects against VEGF inhibitor-induced glomerular endothelial and podocyte injury |
title_sort | protease-activated receptor 2 protects against vegf inhibitor-induced glomerular endothelial and podocyte injury |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6393426/ https://www.ncbi.nlm.nih.gov/pubmed/30814628 http://dx.doi.org/10.1038/s41598-019-39914-8 |
work_keys_str_mv | AT oeyuji proteaseactivatedreceptor2protectsagainstvegfinhibitorinducedglomerularendothelialandpodocyteinjury AT fushimatomofumi proteaseactivatedreceptor2protectsagainstvegfinhibitorinducedglomerularendothelialandpodocyteinjury AT satoemiko proteaseactivatedreceptor2protectsagainstvegfinhibitorinducedglomerularendothelialandpodocyteinjury AT sekimotoakiyo proteaseactivatedreceptor2protectsagainstvegfinhibitorinducedglomerularendothelialandpodocyteinjury AT kisukiyomi proteaseactivatedreceptor2protectsagainstvegfinhibitorinducedglomerularendothelialandpodocyteinjury AT satohiroshi proteaseactivatedreceptor2protectsagainstvegfinhibitorinducedglomerularendothelialandpodocyteinjury AT sugawarajunichi proteaseactivatedreceptor2protectsagainstvegfinhibitorinducedglomerularendothelialandpodocyteinjury AT itosadayoshi proteaseactivatedreceptor2protectsagainstvegfinhibitorinducedglomerularendothelialandpodocyteinjury AT takahashinobuyuki proteaseactivatedreceptor2protectsagainstvegfinhibitorinducedglomerularendothelialandpodocyteinjury |