Study of the Role of the Tyrosine Kinase Receptor MerTK in the Development of Kidney Ischemia-Reperfusion Injury in RCS Rats

Renal ischaemia reperfusion (I/R) triggers a cascade of events including oxidative stress, apoptotic body and microparticle (MP) formation as well as an acute inflammatory process that may contribute to organ failure. Macrophages are recruited to phagocytose cell debris and MPs. The tyrosine kinase...

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Autores principales:	Thomas Pelé, Sebastien Giraud, Sandrine Joffrion, Virginie Ameteau, Adriana Delwail, Jean-Michel Goujon, Laurent Macchi, Thierry Hauet, Fatima Dkhissi, Omar Benzakour
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	ischemia-reperfusion MerTK microparticles inflammation phagocytosis RCS rats Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/246ae4107c5e4f28960688bbb808a594
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spelling	oai:doaj.org-article:246ae4107c5e4f28960688bbb808a5942021-11-25T17:53:26ZStudy of the Role of the Tyrosine Kinase Receptor MerTK in the Development of Kidney Ischemia-Reperfusion Injury in RCS Rats10.3390/ijms2222121031422-00671661-6596https://doaj.org/article/246ae4107c5e4f28960688bbb808a5942021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12103https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Renal ischaemia reperfusion (I/R) triggers a cascade of events including oxidative stress, apoptotic body and microparticle (MP) formation as well as an acute inflammatory process that may contribute to organ failure. Macrophages are recruited to phagocytose cell debris and MPs. The tyrosine kinase receptor MerTK is a major player in the phagocytosis process. Experimental models of renal I/R events are of major importance for identifying I/R key players and for elaborating novel therapeutical approaches. A major aim of our study was to investigate possible involvement of MerTK in renal I/R. We performed our study on both natural mutant rats for MerTK (referred to as RCS) and on wild type rats referred to as WT. I/R was established by of bilateral clamping of the renal pedicles for 30′ followed by three days of reperfusion. Plasma samples were analysed for creatinine, aspartate aminotransferase (ASAT), lactate dehydrogenase (LDH), kidney injury molecule -1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) levels and for MPs. Kidney tissue damage and CD68-positive cell requirement were analysed by histochemistry. monocyte chemoattractant protein-1 (MCP-1), myeloperoxidase (MPO), inducible nitric oxide synthase (iNOS), and histone 3A (H3A) levels in kidney tissue lysates were analysed by western blotting. The phagocytic activity of blood-isolated monocytes collected from RCS or WT towards annexin-V positive bodies derived from cultured renal cell was assessed by fluorescence-activated single cell sorting (FACS) and confocal microscopy analyses. The renal I/R model for RCS rat described for the first time here paves the way for further investigations of MerTK-dependent events in renal tissue injury and repair mechanisms.Thomas PeléSebastien GiraudSandrine JoffrionVirginie AmeteauAdriana DelwailJean-Michel GoujonLaurent MacchiThierry HauetFatima DkhissiOmar BenzakourMDPI AGarticleischemia-reperfusionMerTKmicroparticlesinflammationphagocytosisRCS ratsBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12103, p 12103 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ischemia-reperfusion MerTK microparticles inflammation phagocytosis RCS rats Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	ischemia-reperfusion MerTK microparticles inflammation phagocytosis RCS rats Biology (General) QH301-705.5 Chemistry QD1-999 Thomas Pelé Sebastien Giraud Sandrine Joffrion Virginie Ameteau Adriana Delwail Jean-Michel Goujon Laurent Macchi Thierry Hauet Fatima Dkhissi Omar Benzakour Study of the Role of the Tyrosine Kinase Receptor MerTK in the Development of Kidney Ischemia-Reperfusion Injury in RCS Rats
description	Renal ischaemia reperfusion (I/R) triggers a cascade of events including oxidative stress, apoptotic body and microparticle (MP) formation as well as an acute inflammatory process that may contribute to organ failure. Macrophages are recruited to phagocytose cell debris and MPs. The tyrosine kinase receptor MerTK is a major player in the phagocytosis process. Experimental models of renal I/R events are of major importance for identifying I/R key players and for elaborating novel therapeutical approaches. A major aim of our study was to investigate possible involvement of MerTK in renal I/R. We performed our study on both natural mutant rats for MerTK (referred to as RCS) and on wild type rats referred to as WT. I/R was established by of bilateral clamping of the renal pedicles for 30′ followed by three days of reperfusion. Plasma samples were analysed for creatinine, aspartate aminotransferase (ASAT), lactate dehydrogenase (LDH), kidney injury molecule -1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) levels and for MPs. Kidney tissue damage and CD68-positive cell requirement were analysed by histochemistry. monocyte chemoattractant protein-1 (MCP-1), myeloperoxidase (MPO), inducible nitric oxide synthase (iNOS), and histone 3A (H3A) levels in kidney tissue lysates were analysed by western blotting. The phagocytic activity of blood-isolated monocytes collected from RCS or WT towards annexin-V positive bodies derived from cultured renal cell was assessed by fluorescence-activated single cell sorting (FACS) and confocal microscopy analyses. The renal I/R model for RCS rat described for the first time here paves the way for further investigations of MerTK-dependent events in renal tissue injury and repair mechanisms.
format	article
author	Thomas Pelé Sebastien Giraud Sandrine Joffrion Virginie Ameteau Adriana Delwail Jean-Michel Goujon Laurent Macchi Thierry Hauet Fatima Dkhissi Omar Benzakour
author_facet	Thomas Pelé Sebastien Giraud Sandrine Joffrion Virginie Ameteau Adriana Delwail Jean-Michel Goujon Laurent Macchi Thierry Hauet Fatima Dkhissi Omar Benzakour
author_sort	Thomas Pelé
title	Study of the Role of the Tyrosine Kinase Receptor MerTK in the Development of Kidney Ischemia-Reperfusion Injury in RCS Rats
title_short	Study of the Role of the Tyrosine Kinase Receptor MerTK in the Development of Kidney Ischemia-Reperfusion Injury in RCS Rats
title_full	Study of the Role of the Tyrosine Kinase Receptor MerTK in the Development of Kidney Ischemia-Reperfusion Injury in RCS Rats
title_fullStr	Study of the Role of the Tyrosine Kinase Receptor MerTK in the Development of Kidney Ischemia-Reperfusion Injury in RCS Rats
title_full_unstemmed	Study of the Role of the Tyrosine Kinase Receptor MerTK in the Development of Kidney Ischemia-Reperfusion Injury in RCS Rats
title_sort	study of the role of the tyrosine kinase receptor mertk in the development of kidney ischemia-reperfusion injury in rcs rats
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/246ae4107c5e4f28960688bbb808a594
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Study of the Role of the Tyrosine Kinase Receptor MerTK in the Development of Kidney Ischemia-Reperfusion Injury in RCS Rats

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