Thrombomodulin is upregulated in the kidneys of women with pre-eclampsia

Abstract The endothelial glycoprotein thrombomodulin regulates coagulation, vascular inflammation and apoptosis. In the kidney, thrombomodulin protects the glomerular filtration barrier by eliciting crosstalk between the glomerular endothelium and podocytes. Several glomerular pathologies are charac...

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Autores principales:	Cleo C. L. van Aanhold, Manon Bos, Katrina M. Mirabito Colafella, Marie-Louise P. van der Hoorn, Ron Wolterbeek, Jan A. Bruijn, Kitty W. M. Bloemenkamp, Anton H. van den Meiracker, A. H. Jan Danser, Hans J. Baelde
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b5a3c50f5a64483389c49689efbff347
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spelling	oai:doaj.org-article:b5a3c50f5a64483389c49689efbff3472021-12-02T11:37:23ZThrombomodulin is upregulated in the kidneys of women with pre-eclampsia10.1038/s41598-021-85040-92045-2322https://doaj.org/article/b5a3c50f5a64483389c49689efbff3472021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85040-9https://doaj.org/toc/2045-2322Abstract The endothelial glycoprotein thrombomodulin regulates coagulation, vascular inflammation and apoptosis. In the kidney, thrombomodulin protects the glomerular filtration barrier by eliciting crosstalk between the glomerular endothelium and podocytes. Several glomerular pathologies are characterized by a loss of glomerular thrombomodulin. In women with pre-eclampsia, serum levels of soluble thrombomodulin are increased, possibly reflecting a loss from the glomerular endothelium. We set out to investigate whether thrombomodulin expression is decreased in the kidneys of women with pre-eclampsia and rats exposed to an angiogenesis inhibitor. Thrombomodulin expression was examined using immunohistochemistry and qPCR in renal autopsy tissues collected from 11 pre-eclamptic women, 22 pregnant controls and 11 hypertensive non-pregnant women. Further, kidneys from rats treated with increasing doses of sunitinib or sunitinib in combination with endothelin receptor antagonists were studied. Glomerular thrombomodulin protein levels were increased in the kidneys of women with pre-eclampsia. In parallel, in rats exposed to sunitinib, glomerular thrombomodulin was upregulated in a dose-dependent manner, and the upregulation of glomerular thrombomodulin preceded the onset of histopathological changes. Selective ETAR blockade, but not dual ETA/BR blockade, normalised the sunitinib-induced increase in thrombomodulin expression and albuminuria. We propose that glomerular thrombomodulin expression increases at an early stage of renal damage induced by antiangiogenic conditions. The upregulation of this nephroprotective protein in glomerular endothelial cells might serve as a mechanism to protect the glomerular filtration barrier in pre-eclampsia.Cleo C. L. van AanholdManon BosKatrina M. Mirabito ColafellaMarie-Louise P. van der HoornRon WolterbeekJan A. BruijnKitty W. M. BloemenkampAnton H. van den MeirackerA. H. Jan DanserHans J. BaeldeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Cleo C. L. van Aanhold Manon Bos Katrina M. Mirabito Colafella Marie-Louise P. van der Hoorn Ron Wolterbeek Jan A. Bruijn Kitty W. M. Bloemenkamp Anton H. van den Meiracker A. H. Jan Danser Hans J. Baelde Thrombomodulin is upregulated in the kidneys of women with pre-eclampsia
description	Abstract The endothelial glycoprotein thrombomodulin regulates coagulation, vascular inflammation and apoptosis. In the kidney, thrombomodulin protects the glomerular filtration barrier by eliciting crosstalk between the glomerular endothelium and podocytes. Several glomerular pathologies are characterized by a loss of glomerular thrombomodulin. In women with pre-eclampsia, serum levels of soluble thrombomodulin are increased, possibly reflecting a loss from the glomerular endothelium. We set out to investigate whether thrombomodulin expression is decreased in the kidneys of women with pre-eclampsia and rats exposed to an angiogenesis inhibitor. Thrombomodulin expression was examined using immunohistochemistry and qPCR in renal autopsy tissues collected from 11 pre-eclamptic women, 22 pregnant controls and 11 hypertensive non-pregnant women. Further, kidneys from rats treated with increasing doses of sunitinib or sunitinib in combination with endothelin receptor antagonists were studied. Glomerular thrombomodulin protein levels were increased in the kidneys of women with pre-eclampsia. In parallel, in rats exposed to sunitinib, glomerular thrombomodulin was upregulated in a dose-dependent manner, and the upregulation of glomerular thrombomodulin preceded the onset of histopathological changes. Selective ETAR blockade, but not dual ETA/BR blockade, normalised the sunitinib-induced increase in thrombomodulin expression and albuminuria. We propose that glomerular thrombomodulin expression increases at an early stage of renal damage induced by antiangiogenic conditions. The upregulation of this nephroprotective protein in glomerular endothelial cells might serve as a mechanism to protect the glomerular filtration barrier in pre-eclampsia.
format	article
author	Cleo C. L. van Aanhold Manon Bos Katrina M. Mirabito Colafella Marie-Louise P. van der Hoorn Ron Wolterbeek Jan A. Bruijn Kitty W. M. Bloemenkamp Anton H. van den Meiracker A. H. Jan Danser Hans J. Baelde
author_facet	Cleo C. L. van Aanhold Manon Bos Katrina M. Mirabito Colafella Marie-Louise P. van der Hoorn Ron Wolterbeek Jan A. Bruijn Kitty W. M. Bloemenkamp Anton H. van den Meiracker A. H. Jan Danser Hans J. Baelde
author_sort	Cleo C. L. van Aanhold
title	Thrombomodulin is upregulated in the kidneys of women with pre-eclampsia
title_short	Thrombomodulin is upregulated in the kidneys of women with pre-eclampsia
title_full	Thrombomodulin is upregulated in the kidneys of women with pre-eclampsia
title_fullStr	Thrombomodulin is upregulated in the kidneys of women with pre-eclampsia
title_full_unstemmed	Thrombomodulin is upregulated in the kidneys of women with pre-eclampsia
title_sort	thrombomodulin is upregulated in the kidneys of women with pre-eclampsia
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/b5a3c50f5a64483389c49689efbff347
work_keys_str_mv	AT cleoclvanaanhold thrombomodulinisupregulatedinthekidneysofwomenwithpreeclampsia AT manonbos thrombomodulinisupregulatedinthekidneysofwomenwithpreeclampsia AT katrinammirabitocolafella thrombomodulinisupregulatedinthekidneysofwomenwithpreeclampsia AT marielouisepvanderhoorn thrombomodulinisupregulatedinthekidneysofwomenwithpreeclampsia AT ronwolterbeek thrombomodulinisupregulatedinthekidneysofwomenwithpreeclampsia AT janabruijn thrombomodulinisupregulatedinthekidneysofwomenwithpreeclampsia AT kittywmbloemenkamp thrombomodulinisupregulatedinthekidneysofwomenwithpreeclampsia AT antonhvandenmeiracker thrombomodulinisupregulatedinthekidneysofwomenwithpreeclampsia AT ahjandanser thrombomodulinisupregulatedinthekidneysofwomenwithpreeclampsia AT hansjbaelde thrombomodulinisupregulatedinthekidneysofwomenwithpreeclampsia
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Thrombomodulin is upregulated in the kidneys of women with pre-eclampsia

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