Deletion of TLR4 reduces apoptosis and improves histology in a murine kidney transplant model

Abstract Acute kidney injury (AKI) after transplantation of human deceased donor kidneys is associated with upregulation of tubular toll like receptor 4 (TLR4), but whether TLR4 is required for AKI is unknown. We hypothesized that TLR4 knockout mice (TLR4KO) subjected to cold ischemia followed by ki...

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Autores principales:	Swati Jain, Robert Plenter, Trevor Nydam, Ronald G. Gill, Alkesh Jani
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6651c1c55f124889a4a21bbb3cb3d3e9
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spelling	oai:doaj.org-article:6651c1c55f124889a4a21bbb3cb3d3e92021-12-02T18:51:01ZDeletion of TLR4 reduces apoptosis and improves histology in a murine kidney transplant model10.1038/s41598-021-95504-72045-2322https://doaj.org/article/6651c1c55f124889a4a21bbb3cb3d3e92021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95504-7https://doaj.org/toc/2045-2322Abstract Acute kidney injury (AKI) after transplantation of human deceased donor kidneys is associated with upregulation of tubular toll like receptor 4 (TLR4), but whether TLR4 is required for AKI is unknown. We hypothesized that TLR4 knockout mice (TLR4KO) subjected to cold ischemia followed by kidney transplant (CI + Txp) would be protected from AKI. C57Bl/6J wild type or TLR4KO kidneys were subjected to CI + Txp into wild type recipients. Tubular cell apoptosis, tubular injury and cast formation were significantly improved in recipients of TLR4KO kidneys. TLR4KO kidneys also demonstrated significantly decreased expression of the effector caspase 8. Brush border injury scores and serum creatinine were not different in recipients of TLR4KO versus wild type kidneys. Phosphorylated RIP3 and MLKL through which TLR4 signals programmed necrosis were expressed in both recipient groups. In addition, TNF-α and TNFR1 expression were significantly increased in recipient serum and TLR4KO kidneys respectively after CI + Txp, suggesting continued activation of programmed necrosis despite TLR4 deletion. Our results suggest that TLR4 deletion decreases apoptosis via inhibition of the death receptor pathway and decreases tubular injury and cast formation.Swati JainRobert PlenterTrevor NydamRonald G. GillAlkesh JaniNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Swati Jain Robert Plenter Trevor Nydam Ronald G. Gill Alkesh Jani Deletion of TLR4 reduces apoptosis and improves histology in a murine kidney transplant model
description	Abstract Acute kidney injury (AKI) after transplantation of human deceased donor kidneys is associated with upregulation of tubular toll like receptor 4 (TLR4), but whether TLR4 is required for AKI is unknown. We hypothesized that TLR4 knockout mice (TLR4KO) subjected to cold ischemia followed by kidney transplant (CI + Txp) would be protected from AKI. C57Bl/6J wild type or TLR4KO kidneys were subjected to CI + Txp into wild type recipients. Tubular cell apoptosis, tubular injury and cast formation were significantly improved in recipients of TLR4KO kidneys. TLR4KO kidneys also demonstrated significantly decreased expression of the effector caspase 8. Brush border injury scores and serum creatinine were not different in recipients of TLR4KO versus wild type kidneys. Phosphorylated RIP3 and MLKL through which TLR4 signals programmed necrosis were expressed in both recipient groups. In addition, TNF-α and TNFR1 expression were significantly increased in recipient serum and TLR4KO kidneys respectively after CI + Txp, suggesting continued activation of programmed necrosis despite TLR4 deletion. Our results suggest that TLR4 deletion decreases apoptosis via inhibition of the death receptor pathway and decreases tubular injury and cast formation.
format	article
author	Swati Jain Robert Plenter Trevor Nydam Ronald G. Gill Alkesh Jani
author_facet	Swati Jain Robert Plenter Trevor Nydam Ronald G. Gill Alkesh Jani
author_sort	Swati Jain
title	Deletion of TLR4 reduces apoptosis and improves histology in a murine kidney transplant model
title_short	Deletion of TLR4 reduces apoptosis and improves histology in a murine kidney transplant model
title_full	Deletion of TLR4 reduces apoptosis and improves histology in a murine kidney transplant model
title_fullStr	Deletion of TLR4 reduces apoptosis and improves histology in a murine kidney transplant model
title_full_unstemmed	Deletion of TLR4 reduces apoptosis and improves histology in a murine kidney transplant model
title_sort	deletion of tlr4 reduces apoptosis and improves histology in a murine kidney transplant model
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/6651c1c55f124889a4a21bbb3cb3d3e9
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Deletion of TLR4 reduces apoptosis and improves histology in a murine kidney transplant model

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