Glomerular endothelial derived vesicles mediate podocyte dysfunction: A potential role for miRNA.

MicroRNAs (miRNA) are shown to be involved in the progression of several types of kidney diseases. Podocytes maintain the integrity of the glomerular basement membrane. Extracellular vesicles (EV) are important in cell-to-cell communication as they can transfer cellular content between cells, includ...

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Autores principales:	N Hill, D L Michell, M Ramirez-Solano, Q Sheng, C Pusey, K C Vickers, K J Woollard
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/df6a7c07993f48308d266e4cda726d95
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spelling	oai:doaj.org-article:df6a7c07993f48308d266e4cda726d952021-12-02T20:05:47ZGlomerular endothelial derived vesicles mediate podocyte dysfunction: A potential role for miRNA.1932-620310.1371/journal.pone.0224852https://doaj.org/article/df6a7c07993f48308d266e4cda726d952020-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0224852https://doaj.org/toc/1932-6203MicroRNAs (miRNA) are shown to be involved in the progression of several types of kidney diseases. Podocytes maintain the integrity of the glomerular basement membrane. Extracellular vesicles (EV) are important in cell-to-cell communication as they can transfer cellular content between cells, including miRNA. However, little is known about how extracellular signals from the glomerular microenvironment regulate podocyte activity. Using a non-contact transwell system, communication between glomerular endothelial cells (GEnC) and podocytes was characterised in-vitro. Identification of transferred EV-miRNAs from GEnC to podocytes was performed using fluorescence cell tracking and miRNA mimetics. To represent kidney disease, podocyte molecular profiling and functions were analysed after EV treatments derived from steady state or activated GEnC. Our data shows activation of GEnC alters EV-miRNA loading, but activation was not found to alter EV secretion. EV delivery of miRNA to recipient podocytes altered cellular miRNA abundance and effector functions in podocytes, including decreased secretion of VEGF and increased mitochondrial stress which lead to altered cellular metabolism and cytoskeletal rearrangement. Finally, results support our hypothesis that miRNA-200c-3p is transfered by EVs from GEnC to podocytes in response to activation, ultimately leading to podocyte dysfunction.N HillD L MichellM Ramirez-SolanoQ ShengC PuseyK C VickersK J WoollardPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 15, Iss 3, p e0224852 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q N Hill D L Michell M Ramirez-Solano Q Sheng C Pusey K C Vickers K J Woollard Glomerular endothelial derived vesicles mediate podocyte dysfunction: A potential role for miRNA.
description	MicroRNAs (miRNA) are shown to be involved in the progression of several types of kidney diseases. Podocytes maintain the integrity of the glomerular basement membrane. Extracellular vesicles (EV) are important in cell-to-cell communication as they can transfer cellular content between cells, including miRNA. However, little is known about how extracellular signals from the glomerular microenvironment regulate podocyte activity. Using a non-contact transwell system, communication between glomerular endothelial cells (GEnC) and podocytes was characterised in-vitro. Identification of transferred EV-miRNAs from GEnC to podocytes was performed using fluorescence cell tracking and miRNA mimetics. To represent kidney disease, podocyte molecular profiling and functions were analysed after EV treatments derived from steady state or activated GEnC. Our data shows activation of GEnC alters EV-miRNA loading, but activation was not found to alter EV secretion. EV delivery of miRNA to recipient podocytes altered cellular miRNA abundance and effector functions in podocytes, including decreased secretion of VEGF and increased mitochondrial stress which lead to altered cellular metabolism and cytoskeletal rearrangement. Finally, results support our hypothesis that miRNA-200c-3p is transfered by EVs from GEnC to podocytes in response to activation, ultimately leading to podocyte dysfunction.
format	article
author	N Hill D L Michell M Ramirez-Solano Q Sheng C Pusey K C Vickers K J Woollard
author_facet	N Hill D L Michell M Ramirez-Solano Q Sheng C Pusey K C Vickers K J Woollard
author_sort	N Hill
title	Glomerular endothelial derived vesicles mediate podocyte dysfunction: A potential role for miRNA.
title_short	Glomerular endothelial derived vesicles mediate podocyte dysfunction: A potential role for miRNA.
title_full	Glomerular endothelial derived vesicles mediate podocyte dysfunction: A potential role for miRNA.
title_fullStr	Glomerular endothelial derived vesicles mediate podocyte dysfunction: A potential role for miRNA.
title_full_unstemmed	Glomerular endothelial derived vesicles mediate podocyte dysfunction: A potential role for miRNA.
title_sort	glomerular endothelial derived vesicles mediate podocyte dysfunction: a potential role for mirna.
publisher	Public Library of Science (PLoS)
publishDate	2020
url	https://doaj.org/article/df6a7c07993f48308d266e4cda726d95
work_keys_str_mv	AT nhill glomerularendothelialderivedvesiclesmediatepodocytedysfunctionapotentialroleformirna AT dlmichell glomerularendothelialderivedvesiclesmediatepodocytedysfunctionapotentialroleformirna AT mramirezsolano glomerularendothelialderivedvesiclesmediatepodocytedysfunctionapotentialroleformirna AT qsheng glomerularendothelialderivedvesiclesmediatepodocytedysfunctionapotentialroleformirna AT cpusey glomerularendothelialderivedvesiclesmediatepodocytedysfunctionapotentialroleformirna AT kcvickers glomerularendothelialderivedvesiclesmediatepodocytedysfunctionapotentialroleformirna AT kjwoollard glomerularendothelialderivedvesiclesmediatepodocytedysfunctionapotentialroleformirna
_version_	1718375455697928192

Glomerular endothelial derived vesicles mediate podocyte dysfunction: A potential role for miRNA.

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