Exploring the mechanism of hyperpermeability following glycocalyx degradation: Beyond the glycocalyx as a structural barrier.

Pathological hyperpermeability is a morbidity involved in various systemic diseases, including sepsis. The endothelial glycocalyx layer (GCX) plays a key role in controlling vascular permeability and could be a useful therapeutic target. The purpose of the present study was to analyze the functional...

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Autores principales:	Kyoko Abe, Junichi Tanaka, Kenji Mishima, Takehiko Iijima
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2be6538a869846e88547e93f46d08bee
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spelling	oai:doaj.org-article:2be6538a869846e88547e93f46d08bee2021-11-25T06:23:35ZExploring the mechanism of hyperpermeability following glycocalyx degradation: Beyond the glycocalyx as a structural barrier.1932-620310.1371/journal.pone.0252416https://doaj.org/article/2be6538a869846e88547e93f46d08bee2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0252416https://doaj.org/toc/1932-6203Pathological hyperpermeability is a morbidity involved in various systemic diseases, including sepsis. The endothelial glycocalyx layer (GCX) plays a key role in controlling vascular permeability and could be a useful therapeutic target. The purpose of the present study was to analyze the functional role of the GCX in vascular permeability and to elucidate its role in pathological conditions. First, male C57BL/6J wild-type mice were used as in vivo models to study the effects of sepsis and the pharmacological digestion of glycosaminoglycans (GAGs) on the GCX. Vascular permeability was evaluated using fluorescein isothiocyanate (FITC)-labeled dextran. Second, the changes in gene expression in vascular endothelial cells after GAGs digestion were compared between a control and a septic model using RNA sequencing. In the in vivo study, the glycocalyx was depleted in both the septic model and the group with pharmacological GAGs digestion. FITC-labeled dextran had leaked into the interstitium in the septic group, but not in the other groups. In the in vitro study, histamine decreased the transendothelial electrical resistance (TEER), indicating an increase in permeability. GAGs digestion alone did not change the TEER, and the effect of histamine on the TEER was not enhanced by GAGs digestion. The gene expression profiles after GAGs digestion differed from the control condition, indicating the initiation of signal transduction. In conclusion, we demonstrated that the structural barrier of the GCX does not solely determine the fluid permeability of the endothelial layer, since enzymatic depletion of the GCX did not increase the permeability. The gene expression findings suggest that the digestion of GAGs alone did not induce hyperpermeability either in vitro or in vivo, although sepsis did induce hyperpermeability. While GAGs degradation by itself does not appear to induce hyperpermeability, it may play an important role in initiating signal transductions.Kyoko AbeJunichi TanakaKenji MishimaTakehiko IijimaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 6, p e0252416 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kyoko Abe Junichi Tanaka Kenji Mishima Takehiko Iijima Exploring the mechanism of hyperpermeability following glycocalyx degradation: Beyond the glycocalyx as a structural barrier.
description	Pathological hyperpermeability is a morbidity involved in various systemic diseases, including sepsis. The endothelial glycocalyx layer (GCX) plays a key role in controlling vascular permeability and could be a useful therapeutic target. The purpose of the present study was to analyze the functional role of the GCX in vascular permeability and to elucidate its role in pathological conditions. First, male C57BL/6J wild-type mice were used as in vivo models to study the effects of sepsis and the pharmacological digestion of glycosaminoglycans (GAGs) on the GCX. Vascular permeability was evaluated using fluorescein isothiocyanate (FITC)-labeled dextran. Second, the changes in gene expression in vascular endothelial cells after GAGs digestion were compared between a control and a septic model using RNA sequencing. In the in vivo study, the glycocalyx was depleted in both the septic model and the group with pharmacological GAGs digestion. FITC-labeled dextran had leaked into the interstitium in the septic group, but not in the other groups. In the in vitro study, histamine decreased the transendothelial electrical resistance (TEER), indicating an increase in permeability. GAGs digestion alone did not change the TEER, and the effect of histamine on the TEER was not enhanced by GAGs digestion. The gene expression profiles after GAGs digestion differed from the control condition, indicating the initiation of signal transduction. In conclusion, we demonstrated that the structural barrier of the GCX does not solely determine the fluid permeability of the endothelial layer, since enzymatic depletion of the GCX did not increase the permeability. The gene expression findings suggest that the digestion of GAGs alone did not induce hyperpermeability either in vitro or in vivo, although sepsis did induce hyperpermeability. While GAGs degradation by itself does not appear to induce hyperpermeability, it may play an important role in initiating signal transductions.
format	article
author	Kyoko Abe Junichi Tanaka Kenji Mishima Takehiko Iijima
author_facet	Kyoko Abe Junichi Tanaka Kenji Mishima Takehiko Iijima
author_sort	Kyoko Abe
title	Exploring the mechanism of hyperpermeability following glycocalyx degradation: Beyond the glycocalyx as a structural barrier.
title_short	Exploring the mechanism of hyperpermeability following glycocalyx degradation: Beyond the glycocalyx as a structural barrier.
title_full	Exploring the mechanism of hyperpermeability following glycocalyx degradation: Beyond the glycocalyx as a structural barrier.
title_fullStr	Exploring the mechanism of hyperpermeability following glycocalyx degradation: Beyond the glycocalyx as a structural barrier.
title_full_unstemmed	Exploring the mechanism of hyperpermeability following glycocalyx degradation: Beyond the glycocalyx as a structural barrier.
title_sort	exploring the mechanism of hyperpermeability following glycocalyx degradation: beyond the glycocalyx as a structural barrier.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/2be6538a869846e88547e93f46d08bee
work_keys_str_mv	AT kyokoabe exploringthemechanismofhyperpermeabilityfollowingglycocalyxdegradationbeyondtheglycocalyxasastructuralbarrier AT junichitanaka exploringthemechanismofhyperpermeabilityfollowingglycocalyxdegradationbeyondtheglycocalyxasastructuralbarrier AT kenjimishima exploringthemechanismofhyperpermeabilityfollowingglycocalyxdegradationbeyondtheglycocalyxasastructuralbarrier AT takehikoiijima exploringthemechanismofhyperpermeabilityfollowingglycocalyxdegradationbeyondtheglycocalyxasastructuralbarrier
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Exploring the mechanism of hyperpermeability following glycocalyx degradation: Beyond the glycocalyx as a structural barrier.

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