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Esaxerenone Inhibits Renal Angiogenesis and Endothelial-Mesenchymal Transition via the VEGFA and TGF-β1 Pathways in Aldosterone-Infused Mice

Renal fibrosis is an inevitable process in the progression of chronic kidney disease (CKD). Angiogenesis plays an important role in this process. Vascular endothelial cells are involved in renal fibrosis by phenotypic transformation and secretion of extracellular matrix. Aldosterone stimulates miner...

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Autores principales: Gao, Xiaomeng, Chang, Jingyue, Chang, Yi, Fan, Lili, Liu, Ziqian, Zhang, Cuijuan, Shimosawa, Tatsuo, Yang, Fan, Xu, Qingyou
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10380380/
https://www.ncbi.nlm.nih.gov/pubmed/37511521
http://dx.doi.org/10.3390/ijms241411766
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author Gao, Xiaomeng
Chang, Jingyue
Chang, Yi
Fan, Lili
Liu, Ziqian
Zhang, Cuijuan
Shimosawa, Tatsuo
Yang, Fan
Xu, Qingyou
author_facet Gao, Xiaomeng
Chang, Jingyue
Chang, Yi
Fan, Lili
Liu, Ziqian
Zhang, Cuijuan
Shimosawa, Tatsuo
Yang, Fan
Xu, Qingyou
author_sort Gao, Xiaomeng
collection PubMed
description Renal fibrosis is an inevitable process in the progression of chronic kidney disease (CKD). Angiogenesis plays an important role in this process. Vascular endothelial cells are involved in renal fibrosis by phenotypic transformation and secretion of extracellular matrix. Aldosterone stimulates mineralocorticoid receptor (MR) activation and induces inflammation, which is important for angiogenesis. Clinically, MR blockers (MRBs) have a protective effect on damaged kidneys, which may be associated with inhibition of angiogenesis. In this study, we used aldosterone-infused mice and found that aldosterone induced angiogenesis and that endothelial-mesenchymal transition (EndMT) in neovascular endothelial cells was involved in renal fibrosis. Notably, aldosterone induced inflammation and stimulated macrophages to secrete vascular endothelial growth factor (VEGF) A to regulate angiogenesis by activating MR, whereas EndMT occurred in response to transforming growth factor-β1 (TGF-β1) induction and participated in renal fibrosis. These effects were antagonized by the MRB esaxerenone. These findings suggest that reducing angiogenesis may be an effective strategy for treating renal fibrosis.
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spelling pubmed-103803802023-07-29 Esaxerenone Inhibits Renal Angiogenesis and Endothelial-Mesenchymal Transition via the VEGFA and TGF-β1 Pathways in Aldosterone-Infused Mice Gao, Xiaomeng Chang, Jingyue Chang, Yi Fan, Lili Liu, Ziqian Zhang, Cuijuan Shimosawa, Tatsuo Yang, Fan Xu, Qingyou Int J Mol Sci Article Renal fibrosis is an inevitable process in the progression of chronic kidney disease (CKD). Angiogenesis plays an important role in this process. Vascular endothelial cells are involved in renal fibrosis by phenotypic transformation and secretion of extracellular matrix. Aldosterone stimulates mineralocorticoid receptor (MR) activation and induces inflammation, which is important for angiogenesis. Clinically, MR blockers (MRBs) have a protective effect on damaged kidneys, which may be associated with inhibition of angiogenesis. In this study, we used aldosterone-infused mice and found that aldosterone induced angiogenesis and that endothelial-mesenchymal transition (EndMT) in neovascular endothelial cells was involved in renal fibrosis. Notably, aldosterone induced inflammation and stimulated macrophages to secrete vascular endothelial growth factor (VEGF) A to regulate angiogenesis by activating MR, whereas EndMT occurred in response to transforming growth factor-β1 (TGF-β1) induction and participated in renal fibrosis. These effects were antagonized by the MRB esaxerenone. These findings suggest that reducing angiogenesis may be an effective strategy for treating renal fibrosis. MDPI 2023-07-21 /pmc/articles/PMC10380380/ /pubmed/37511521 http://dx.doi.org/10.3390/ijms241411766 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gao, Xiaomeng
Chang, Jingyue
Chang, Yi
Fan, Lili
Liu, Ziqian
Zhang, Cuijuan
Shimosawa, Tatsuo
Yang, Fan
Xu, Qingyou
Esaxerenone Inhibits Renal Angiogenesis and Endothelial-Mesenchymal Transition via the VEGFA and TGF-β1 Pathways in Aldosterone-Infused Mice
title Esaxerenone Inhibits Renal Angiogenesis and Endothelial-Mesenchymal Transition via the VEGFA and TGF-β1 Pathways in Aldosterone-Infused Mice
title_full Esaxerenone Inhibits Renal Angiogenesis and Endothelial-Mesenchymal Transition via the VEGFA and TGF-β1 Pathways in Aldosterone-Infused Mice
title_fullStr Esaxerenone Inhibits Renal Angiogenesis and Endothelial-Mesenchymal Transition via the VEGFA and TGF-β1 Pathways in Aldosterone-Infused Mice
title_full_unstemmed Esaxerenone Inhibits Renal Angiogenesis and Endothelial-Mesenchymal Transition via the VEGFA and TGF-β1 Pathways in Aldosterone-Infused Mice
title_short Esaxerenone Inhibits Renal Angiogenesis and Endothelial-Mesenchymal Transition via the VEGFA and TGF-β1 Pathways in Aldosterone-Infused Mice
title_sort esaxerenone inhibits renal angiogenesis and endothelial-mesenchymal transition via the vegfa and tgf-β1 pathways in aldosterone-infused mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10380380/
https://www.ncbi.nlm.nih.gov/pubmed/37511521
http://dx.doi.org/10.3390/ijms241411766
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