Cargando…

Ferroptosis, a new target for treatment of renal injury and fibrosis in a 5/6 nephrectomy-induced CKD rat model

Ferroptosis is a non-traditional form of regulated cell death, characterized by iron overload and lipid peroxidation. Exploration of ferroptosis in chronic kidney disease (CKD) has been extremely limited to date. In this study, we established a rat model of CKD by 5/6 nephrectomy, treated CKD rats w...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Jingyu, Wang, Yaqing, Liu, Yi, Cai, Xintian, Huang, Xin, Fu, Wenjing, Wang, Lei, Qiu, Lihua, Li, Junying, Sun, Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8941123/
https://www.ncbi.nlm.nih.gov/pubmed/35318301
http://dx.doi.org/10.1038/s41420-022-00931-8
_version_ 1784673042073387008
author Wang, Jingyu
Wang, Yaqing
Liu, Yi
Cai, Xintian
Huang, Xin
Fu, Wenjing
Wang, Lei
Qiu, Lihua
Li, Junying
Sun, Li
author_facet Wang, Jingyu
Wang, Yaqing
Liu, Yi
Cai, Xintian
Huang, Xin
Fu, Wenjing
Wang, Lei
Qiu, Lihua
Li, Junying
Sun, Li
author_sort Wang, Jingyu
collection PubMed
description Ferroptosis is a non-traditional form of regulated cell death, characterized by iron overload and lipid peroxidation. Exploration of ferroptosis in chronic kidney disease (CKD) has been extremely limited to date. In this study, we established a rat model of CKD by 5/6 nephrectomy, treated CKD rats with the ferroptosis inducer, cisplatin (CDDP), and the ferroptosis inhibitor, deferoxamine mesylate (DFO), and observed the resulting pathologic changes (injury markers and fibrosis) and ferroptotic biochemical indices. Kidney iron deposition, lipid peroxidation, mitochondrial defects, ferroptosis marker induction, and TUNEL staining positivity were detected in CKD group rats. Further, treatment with CDDP or DFO influenced renal injury and fibrosis by affecting ferroptosis, rather than apoptosis, and ferroptosis occurs in the remnant kidney due to disordered iron metabolism. In conclusion, our study shows for the first time that 5/6 nephrectomy induces ferroptosis in the remnant kidney and clarifies the underlying pathogenesis. Moreover, we demonstrate that ferroptosis is involved in CKD progression and represents a therapeutic target in chronic kidney injury and renal fibrosis.
format Online
Article
Text
id pubmed-8941123
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-89411232022-04-11 Ferroptosis, a new target for treatment of renal injury and fibrosis in a 5/6 nephrectomy-induced CKD rat model Wang, Jingyu Wang, Yaqing Liu, Yi Cai, Xintian Huang, Xin Fu, Wenjing Wang, Lei Qiu, Lihua Li, Junying Sun, Li Cell Death Discov Article Ferroptosis is a non-traditional form of regulated cell death, characterized by iron overload and lipid peroxidation. Exploration of ferroptosis in chronic kidney disease (CKD) has been extremely limited to date. In this study, we established a rat model of CKD by 5/6 nephrectomy, treated CKD rats with the ferroptosis inducer, cisplatin (CDDP), and the ferroptosis inhibitor, deferoxamine mesylate (DFO), and observed the resulting pathologic changes (injury markers and fibrosis) and ferroptotic biochemical indices. Kidney iron deposition, lipid peroxidation, mitochondrial defects, ferroptosis marker induction, and TUNEL staining positivity were detected in CKD group rats. Further, treatment with CDDP or DFO influenced renal injury and fibrosis by affecting ferroptosis, rather than apoptosis, and ferroptosis occurs in the remnant kidney due to disordered iron metabolism. In conclusion, our study shows for the first time that 5/6 nephrectomy induces ferroptosis in the remnant kidney and clarifies the underlying pathogenesis. Moreover, we demonstrate that ferroptosis is involved in CKD progression and represents a therapeutic target in chronic kidney injury and renal fibrosis. Nature Publishing Group UK 2022-03-22 /pmc/articles/PMC8941123/ /pubmed/35318301 http://dx.doi.org/10.1038/s41420-022-00931-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Wang, Jingyu
Wang, Yaqing
Liu, Yi
Cai, Xintian
Huang, Xin
Fu, Wenjing
Wang, Lei
Qiu, Lihua
Li, Junying
Sun, Li
Ferroptosis, a new target for treatment of renal injury and fibrosis in a 5/6 nephrectomy-induced CKD rat model
title Ferroptosis, a new target for treatment of renal injury and fibrosis in a 5/6 nephrectomy-induced CKD rat model
title_full Ferroptosis, a new target for treatment of renal injury and fibrosis in a 5/6 nephrectomy-induced CKD rat model
title_fullStr Ferroptosis, a new target for treatment of renal injury and fibrosis in a 5/6 nephrectomy-induced CKD rat model
title_full_unstemmed Ferroptosis, a new target for treatment of renal injury and fibrosis in a 5/6 nephrectomy-induced CKD rat model
title_short Ferroptosis, a new target for treatment of renal injury and fibrosis in a 5/6 nephrectomy-induced CKD rat model
title_sort ferroptosis, a new target for treatment of renal injury and fibrosis in a 5/6 nephrectomy-induced ckd rat model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8941123/
https://www.ncbi.nlm.nih.gov/pubmed/35318301
http://dx.doi.org/10.1038/s41420-022-00931-8
work_keys_str_mv AT wangjingyu ferroptosisanewtargetfortreatmentofrenalinjuryandfibrosisina56nephrectomyinducedckdratmodel
AT wangyaqing ferroptosisanewtargetfortreatmentofrenalinjuryandfibrosisina56nephrectomyinducedckdratmodel
AT liuyi ferroptosisanewtargetfortreatmentofrenalinjuryandfibrosisina56nephrectomyinducedckdratmodel
AT caixintian ferroptosisanewtargetfortreatmentofrenalinjuryandfibrosisina56nephrectomyinducedckdratmodel
AT huangxin ferroptosisanewtargetfortreatmentofrenalinjuryandfibrosisina56nephrectomyinducedckdratmodel
AT fuwenjing ferroptosisanewtargetfortreatmentofrenalinjuryandfibrosisina56nephrectomyinducedckdratmodel
AT wanglei ferroptosisanewtargetfortreatmentofrenalinjuryandfibrosisina56nephrectomyinducedckdratmodel
AT qiulihua ferroptosisanewtargetfortreatmentofrenalinjuryandfibrosisina56nephrectomyinducedckdratmodel
AT lijunying ferroptosisanewtargetfortreatmentofrenalinjuryandfibrosisina56nephrectomyinducedckdratmodel
AT sunli ferroptosisanewtargetfortreatmentofrenalinjuryandfibrosisina56nephrectomyinducedckdratmodel