Kidney Organoids as a Novel Platform to Evaluate Lipopolysaccharide-Induced Oxidative Stress and Apoptosis in Acute Kidney Injury

Sepsis-associated acute kidney injury (SA-AKI) is a life-threatening syndrome. Lipopolysaccharide (LPS) is a widely used inducer for modeling SA-AKI both in vivo and in vitro. However, due to the innate complexity of the kidney architecture, the mechanisms underlying the pathogenesis of SA-AKI, as w...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Weitao Zhang, Ruochen Qi, Tingting Li, Xuepeng Zhang, Yi Shi, Ming Xu, Tongyu Zhu
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	kidney organoids human pluripotent stem cells sepsis acute kidney injury oxidative stress apoptosis Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/2b359165cc914720b192eff328012d3b
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:2b359165cc914720b192eff328012d3b
record_format	dspace
spelling	oai:doaj.org-article:2b359165cc914720b192eff328012d3b2021-12-01T13:04:52ZKidney Organoids as a Novel Platform to Evaluate Lipopolysaccharide-Induced Oxidative Stress and Apoptosis in Acute Kidney Injury2296-858X10.3389/fmed.2021.766073https://doaj.org/article/2b359165cc914720b192eff328012d3b2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmed.2021.766073/fullhttps://doaj.org/toc/2296-858XSepsis-associated acute kidney injury (SA-AKI) is a life-threatening syndrome. Lipopolysaccharide (LPS) is a widely used inducer for modeling SA-AKI both in vivo and in vitro. However, due to the innate complexity of the kidney architecture, the mechanisms underlying the pathogenesis of SA-AKI, as well as those involved in LPS-induced kidney injury remain to be clarified. Kidney organoids derived from human pluripotent stem cells (hPSCs) act as a model of multiple types of kidney cells in vitro and eliminate potential confounders in vivo. In the current study, we established LPS-induced kidney injury models both in vivo and in human kidney organoids. Kidney function, pathological changes, and markers of oxidative stress were evaluated with/without the presence of methylprednisolone (MP) treatment both in vivo and in vitro. The extent of LPS-induced oxidative stress and apoptosis in kidney organoids was further investigated in vitro. LPS-induced acute kidney injury in mice, together with pathological changes and increased oxidative stress, as well as enhanced apoptosis in kidney cells were evaluated. These phenomena were ameliorated by MP treatment. Experiments in kidney organoids showed that the LPS-induced apoptotic effects occurred mainly in podocytes and proximal tubular cells. Our experiments demonstrated the efficacy of using kidney organoids as a solid platform to study LPS-induced kidney injury. LPS induced oxidative stress as well as apoptosis in kidney cells independently of changes in perfusion or immune cell infiltration. MP treatment partially alleviated LPS-induced injury by reducing kidney cell oxidative stress and apoptosis.Weitao ZhangWeitao ZhangRuochen QiRuochen QiTingting LiTingting LiXuepeng ZhangYi ShiYi ShiMing XuMing XuTongyu ZhuTongyu ZhuFrontiers Media S.A.articlekidney organoidshuman pluripotent stem cellssepsisacute kidney injuryoxidative stressapoptosisMedicine (General)R5-920ENFrontiers in Medicine, Vol 8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	kidney organoids human pluripotent stem cells sepsis acute kidney injury oxidative stress apoptosis Medicine (General) R5-920
spellingShingle	kidney organoids human pluripotent stem cells sepsis acute kidney injury oxidative stress apoptosis Medicine (General) R5-920 Weitao Zhang Weitao Zhang Ruochen Qi Ruochen Qi Tingting Li Tingting Li Xuepeng Zhang Yi Shi Yi Shi Ming Xu Ming Xu Tongyu Zhu Tongyu Zhu Kidney Organoids as a Novel Platform to Evaluate Lipopolysaccharide-Induced Oxidative Stress and Apoptosis in Acute Kidney Injury
description	Sepsis-associated acute kidney injury (SA-AKI) is a life-threatening syndrome. Lipopolysaccharide (LPS) is a widely used inducer for modeling SA-AKI both in vivo and in vitro. However, due to the innate complexity of the kidney architecture, the mechanisms underlying the pathogenesis of SA-AKI, as well as those involved in LPS-induced kidney injury remain to be clarified. Kidney organoids derived from human pluripotent stem cells (hPSCs) act as a model of multiple types of kidney cells in vitro and eliminate potential confounders in vivo. In the current study, we established LPS-induced kidney injury models both in vivo and in human kidney organoids. Kidney function, pathological changes, and markers of oxidative stress were evaluated with/without the presence of methylprednisolone (MP) treatment both in vivo and in vitro. The extent of LPS-induced oxidative stress and apoptosis in kidney organoids was further investigated in vitro. LPS-induced acute kidney injury in mice, together with pathological changes and increased oxidative stress, as well as enhanced apoptosis in kidney cells were evaluated. These phenomena were ameliorated by MP treatment. Experiments in kidney organoids showed that the LPS-induced apoptotic effects occurred mainly in podocytes and proximal tubular cells. Our experiments demonstrated the efficacy of using kidney organoids as a solid platform to study LPS-induced kidney injury. LPS induced oxidative stress as well as apoptosis in kidney cells independently of changes in perfusion or immune cell infiltration. MP treatment partially alleviated LPS-induced injury by reducing kidney cell oxidative stress and apoptosis.
format	article
author	Weitao Zhang Weitao Zhang Ruochen Qi Ruochen Qi Tingting Li Tingting Li Xuepeng Zhang Yi Shi Yi Shi Ming Xu Ming Xu Tongyu Zhu Tongyu Zhu
author_facet	Weitao Zhang Weitao Zhang Ruochen Qi Ruochen Qi Tingting Li Tingting Li Xuepeng Zhang Yi Shi Yi Shi Ming Xu Ming Xu Tongyu Zhu Tongyu Zhu
author_sort	Weitao Zhang
title	Kidney Organoids as a Novel Platform to Evaluate Lipopolysaccharide-Induced Oxidative Stress and Apoptosis in Acute Kidney Injury
title_short	Kidney Organoids as a Novel Platform to Evaluate Lipopolysaccharide-Induced Oxidative Stress and Apoptosis in Acute Kidney Injury
title_full	Kidney Organoids as a Novel Platform to Evaluate Lipopolysaccharide-Induced Oxidative Stress and Apoptosis in Acute Kidney Injury
title_fullStr	Kidney Organoids as a Novel Platform to Evaluate Lipopolysaccharide-Induced Oxidative Stress and Apoptosis in Acute Kidney Injury
title_full_unstemmed	Kidney Organoids as a Novel Platform to Evaluate Lipopolysaccharide-Induced Oxidative Stress and Apoptosis in Acute Kidney Injury
title_sort	kidney organoids as a novel platform to evaluate lipopolysaccharide-induced oxidative stress and apoptosis in acute kidney injury
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/2b359165cc914720b192eff328012d3b
work_keys_str_mv	AT weitaozhang kidneyorganoidsasanovelplatformtoevaluatelipopolysaccharideinducedoxidativestressandapoptosisinacutekidneyinjury AT weitaozhang kidneyorganoidsasanovelplatformtoevaluatelipopolysaccharideinducedoxidativestressandapoptosisinacutekidneyinjury AT ruochenqi kidneyorganoidsasanovelplatformtoevaluatelipopolysaccharideinducedoxidativestressandapoptosisinacutekidneyinjury AT ruochenqi kidneyorganoidsasanovelplatformtoevaluatelipopolysaccharideinducedoxidativestressandapoptosisinacutekidneyinjury AT tingtingli kidneyorganoidsasanovelplatformtoevaluatelipopolysaccharideinducedoxidativestressandapoptosisinacutekidneyinjury AT tingtingli kidneyorganoidsasanovelplatformtoevaluatelipopolysaccharideinducedoxidativestressandapoptosisinacutekidneyinjury AT xuepengzhang kidneyorganoidsasanovelplatformtoevaluatelipopolysaccharideinducedoxidativestressandapoptosisinacutekidneyinjury AT yishi kidneyorganoidsasanovelplatformtoevaluatelipopolysaccharideinducedoxidativestressandapoptosisinacutekidneyinjury AT yishi kidneyorganoidsasanovelplatformtoevaluatelipopolysaccharideinducedoxidativestressandapoptosisinacutekidneyinjury AT mingxu kidneyorganoidsasanovelplatformtoevaluatelipopolysaccharideinducedoxidativestressandapoptosisinacutekidneyinjury AT mingxu kidneyorganoidsasanovelplatformtoevaluatelipopolysaccharideinducedoxidativestressandapoptosisinacutekidneyinjury AT tongyuzhu kidneyorganoidsasanovelplatformtoevaluatelipopolysaccharideinducedoxidativestressandapoptosisinacutekidneyinjury AT tongyuzhu kidneyorganoidsasanovelplatformtoevaluatelipopolysaccharideinducedoxidativestressandapoptosisinacutekidneyinjury
_version_	1718405164630540288

Kidney Organoids as a Novel Platform to Evaluate Lipopolysaccharide-Induced Oxidative Stress and Apoptosis in Acute Kidney Injury

Ejemplares similares