Myeloid cell-derived coagulation tissue factor is associated with renal tubular damage in mice fed an adenine diet

Abstract Patients with chronic kidney disease (CKD) commonly exhibit hypercoagulability. Increased levels of uremic toxins cause thrombogenicity by increasing tissue factor (TF) expression and activating the extrinsic coagulation cascade. TF is induced in monocytes and macrophages under pathological...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Shu Yamakage, Yuji Oe, Emiko Sato, Koji Okamoto, Akiyo Sekimoto, Satoshi Kumakura, Hiroshi Sato, Mai Yoshida, Tasuku Nagasawa, Mariko Miyazaki, Sadayoshi Ito, Nigel Mackman, Nobuyuki Takahashi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/417c4d56cb9f41a1a7c5ffd5485b6f48
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:417c4d56cb9f41a1a7c5ffd5485b6f48
record_format	dspace
spelling	oai:doaj.org-article:417c4d56cb9f41a1a7c5ffd5485b6f482021-12-02T17:47:04ZMyeloid cell-derived coagulation tissue factor is associated with renal tubular damage in mice fed an adenine diet10.1038/s41598-021-91586-52045-2322https://doaj.org/article/417c4d56cb9f41a1a7c5ffd5485b6f482021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91586-5https://doaj.org/toc/2045-2322Abstract Patients with chronic kidney disease (CKD) commonly exhibit hypercoagulability. Increased levels of uremic toxins cause thrombogenicity by increasing tissue factor (TF) expression and activating the extrinsic coagulation cascade. TF is induced in monocytes and macrophages under pathological conditions, such as inflammatory diseases. However, the role of monocyte myeloid cell TF in CKD progression remains unclear. We aimed to clarify this issue, and the present study found that patients with CKD had elevated levels of D-dimer, a marker of fibrin degradation, which was associated with decreased estimated glomerular filtration rate and increased serum levels of uremic toxins, such as indoxyl sulfate. In vitro studies showed that several uremic toxins increased cellular TF levels in monocytic THP-1 cells. Mice with TF specifically deleted in myeloid cells were fed an adenine diet to cause uremic kidney injury. Myeloid TF deletion reduced tubular injury and pro-inflammatory gene expression in the kidneys of adenine-induced CKD but did not improve renal function as measured by plasma creatinine or blood urea nitrogen. Collectively, our findings suggest a novel concept of pathogenesis of coagulation-mediated kidney injury, in which elevated TF levels in monocytes under uremic conditions is partly involved in the development of CKD.Shu YamakageYuji OeEmiko SatoKoji OkamotoAkiyo SekimotoSatoshi KumakuraHiroshi SatoMai YoshidaTasuku NagasawaMariko MiyazakiSadayoshi ItoNigel MackmanNobuyuki TakahashiNature 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 Shu Yamakage Yuji Oe Emiko Sato Koji Okamoto Akiyo Sekimoto Satoshi Kumakura Hiroshi Sato Mai Yoshida Tasuku Nagasawa Mariko Miyazaki Sadayoshi Ito Nigel Mackman Nobuyuki Takahashi Myeloid cell-derived coagulation tissue factor is associated with renal tubular damage in mice fed an adenine diet
description	Abstract Patients with chronic kidney disease (CKD) commonly exhibit hypercoagulability. Increased levels of uremic toxins cause thrombogenicity by increasing tissue factor (TF) expression and activating the extrinsic coagulation cascade. TF is induced in monocytes and macrophages under pathological conditions, such as inflammatory diseases. However, the role of monocyte myeloid cell TF in CKD progression remains unclear. We aimed to clarify this issue, and the present study found that patients with CKD had elevated levels of D-dimer, a marker of fibrin degradation, which was associated with decreased estimated glomerular filtration rate and increased serum levels of uremic toxins, such as indoxyl sulfate. In vitro studies showed that several uremic toxins increased cellular TF levels in monocytic THP-1 cells. Mice with TF specifically deleted in myeloid cells were fed an adenine diet to cause uremic kidney injury. Myeloid TF deletion reduced tubular injury and pro-inflammatory gene expression in the kidneys of adenine-induced CKD but did not improve renal function as measured by plasma creatinine or blood urea nitrogen. Collectively, our findings suggest a novel concept of pathogenesis of coagulation-mediated kidney injury, in which elevated TF levels in monocytes under uremic conditions is partly involved in the development of CKD.
format	article
author	Shu Yamakage Yuji Oe Emiko Sato Koji Okamoto Akiyo Sekimoto Satoshi Kumakura Hiroshi Sato Mai Yoshida Tasuku Nagasawa Mariko Miyazaki Sadayoshi Ito Nigel Mackman Nobuyuki Takahashi
author_facet	Shu Yamakage Yuji Oe Emiko Sato Koji Okamoto Akiyo Sekimoto Satoshi Kumakura Hiroshi Sato Mai Yoshida Tasuku Nagasawa Mariko Miyazaki Sadayoshi Ito Nigel Mackman Nobuyuki Takahashi
author_sort	Shu Yamakage
title	Myeloid cell-derived coagulation tissue factor is associated with renal tubular damage in mice fed an adenine diet
title_short	Myeloid cell-derived coagulation tissue factor is associated with renal tubular damage in mice fed an adenine diet
title_full	Myeloid cell-derived coagulation tissue factor is associated with renal tubular damage in mice fed an adenine diet
title_fullStr	Myeloid cell-derived coagulation tissue factor is associated with renal tubular damage in mice fed an adenine diet
title_full_unstemmed	Myeloid cell-derived coagulation tissue factor is associated with renal tubular damage in mice fed an adenine diet
title_sort	myeloid cell-derived coagulation tissue factor is associated with renal tubular damage in mice fed an adenine diet
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/417c4d56cb9f41a1a7c5ffd5485b6f48
work_keys_str_mv	AT shuyamakage myeloidcellderivedcoagulationtissuefactorisassociatedwithrenaltubulardamageinmicefedanadeninediet AT yujioe myeloidcellderivedcoagulationtissuefactorisassociatedwithrenaltubulardamageinmicefedanadeninediet AT emikosato myeloidcellderivedcoagulationtissuefactorisassociatedwithrenaltubulardamageinmicefedanadeninediet AT kojiokamoto myeloidcellderivedcoagulationtissuefactorisassociatedwithrenaltubulardamageinmicefedanadeninediet AT akiyosekimoto myeloidcellderivedcoagulationtissuefactorisassociatedwithrenaltubulardamageinmicefedanadeninediet AT satoshikumakura myeloidcellderivedcoagulationtissuefactorisassociatedwithrenaltubulardamageinmicefedanadeninediet AT hiroshisato myeloidcellderivedcoagulationtissuefactorisassociatedwithrenaltubulardamageinmicefedanadeninediet AT maiyoshida myeloidcellderivedcoagulationtissuefactorisassociatedwithrenaltubulardamageinmicefedanadeninediet AT tasukunagasawa myeloidcellderivedcoagulationtissuefactorisassociatedwithrenaltubulardamageinmicefedanadeninediet AT marikomiyazaki myeloidcellderivedcoagulationtissuefactorisassociatedwithrenaltubulardamageinmicefedanadeninediet AT sadayoshiito myeloidcellderivedcoagulationtissuefactorisassociatedwithrenaltubulardamageinmicefedanadeninediet AT nigelmackman myeloidcellderivedcoagulationtissuefactorisassociatedwithrenaltubulardamageinmicefedanadeninediet AT nobuyukitakahashi myeloidcellderivedcoagulationtissuefactorisassociatedwithrenaltubulardamageinmicefedanadeninediet
_version_	1718379524882694144

Myeloid cell-derived coagulation tissue factor is associated with renal tubular damage in mice fed an adenine diet

Ejemplares similares