Nguyen, L;
Thewes, L;
Westerhoff, M;
Wruck, W;
Reichert, AS;
Berndt, C;
Adjaye, J;
(2023)
JNK Signalling Regulates Self-Renewal of Proliferative Urine-Derived Renal Progenitor Cells via Inhibition of Ferroptosis.
Cells
, 12
(17)
, Article 2197. 10.3390/cells12172197.
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Abstract
With a global increase in chronic kidney disease patients, alternatives to dialysis and organ transplantation are needed. Stem cell-based therapies could be one possibility to treat chronic kidney disease. Here, we used multipotent urine-derived renal progenitor cells (UdRPCs) to study nephrogenesis. UdRPCs treated with the JNK inhibitor—AEG3482 displayed decreased proliferation and downregulated transcription of cell cycle-associated genes as well as the kidney progenitor markers—SIX2, SALL1 and VCAM1. In addition, levels of activated SMAD2/3, which is associated with the maintenance of self-renewal in UdRPCs, were decreased. JNK inhibition resulted in less efficient oxidative phosphorylation and more lipid peroxidation via ferroptosis, an iron-dependent non-apoptotic cell death pathway linked to various forms of kidney disease. Our study is the first to describe the importance of JNK signalling as a link between maintenance of self-renewal and protection against ferroptosis in SIX2-positive renal progenitor cells.
| Type: | Article |
|---|---|
| Title: | JNK Signalling Regulates Self-Renewal of Proliferative Urine-Derived Renal Progenitor Cells via Inhibition of Ferroptosis |
| Location: | Switzerland |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3390/cells12172197 |
| Publisher version: | https://doi.org/10.3390/cells12172197 |
| Language: | English |
| Additional information: | © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
| Keywords: | JNK signalling, cell death, ferroptosis, mitochondrial metabolism, self-renewal, urine stem cells, Humans, Ferroptosis, Kidney, Renal Dialysis, Renal Insufficiency, Chronic, Stem Cells, MAP Kinase Signaling System |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10179339 |
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