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TUDCA-Treated Mesenchymal Stem Cells Protect against ER Stress in the Hippocampus of a Murine Chronic Kidney Disease Model

1
Department of Pharmacology and Toxicology, University of Alabama at Birmingham School of Medicine, Birmingham, AL 35294, USA
2
Medical Science Research Institute, Soonchunhyang University Seoul Hospital, Seoul 336-745, Korea
3
Departments of Biochemistry, Soonchunhyang University College of Medicine, Cheonan 330-930, Korea
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(3), 613; https://doi.org/10.3390/ijms20030613
Received: 22 December 2018 / Revised: 17 January 2019 / Accepted: 30 January 2019 / Published: 31 January 2019
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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Abstract

Chronic kidney disease (CKD) leads to the loss of kidney function, as well as the dysfunction of several other organs due to the release of uremic toxins into the system. In a murine CKD model, reactive oxygen species (ROS) generation and endoplasmic reticulum (ER) stress are increased in the hippocampus. Mesenchymal stem cells (MSCs) are one of the candidates for cell-based therapy for CKD; however severe pathophysiological conditions can decrease their therapeutic potential. To address these issues, we established tauroursodeoxycholic acid (TUDCA)-treated MSCs using MSCs isolated from patients with CKD (CKD-hMSCs) and assessed the survival and ROS generation of neural cell line SH-SY5Y cells by co-culturing with TUDCA-treated CKD-hMSCs. In the presence of the uremic toxin P-cresol, the death of SH-SY5Y cells was induced by ROS-mediated ER stress. Co-culture with TUDCA-treated CKD-hMSCs increased anti-oxidant enzyme activities in SH-SY5Y cells through the upregulation of the cellular prion protein (PrPC) expression. Upregulated PrPC expression in SH-SY5Y cells protected against CKD-mediated ER stress and apoptosis. In an adenine-induced murine CKD model, injection with TUDCA-treated CKD-hMSCs suppressed ROS generation and ER stress in the hippocampus. These results indicate that TUDCA-treated CKD-hMSCs prevent the CKD-mediated cell death of SH-SY5Y cells by inhibiting ER stress. Our study suggests that treatment with TUDCA could be a powerful strategy for developing autologous MSC-based therapeutics for patients with CKD, and that PrPC might be a pivotal target for protecting neural cells from CKD-mediated ER stress. View Full-Text
Keywords: chronic kidney disease; mesenchymal stem cells; endoplasmic reticulum stress; tauroursodeoxycholic acid; anti-oxidant chronic kidney disease; mesenchymal stem cells; endoplasmic reticulum stress; tauroursodeoxycholic acid; anti-oxidant
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Lee, J.H.; Yoon, Y.M.; Lee, S.H. TUDCA-Treated Mesenchymal Stem Cells Protect against ER Stress in the Hippocampus of a Murine Chronic Kidney Disease Model. Int. J. Mol. Sci. 2019, 20, 613.

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