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Mar. Drugs 2018, 16(4), 121; https://doi.org/10.3390/md16040121

Fucoidan Rescues p-Cresol-Induced Cellular Senescence in Mesenchymal Stem Cells via FAK-Akt-TWIST Axis

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 04401, Korea
3
Departments of Biochemistry, Soonchunhyang University College of Medicine, Cheonan 330-930, Korea
4
Center for Medical Innovation, Seoul National University Hospital, Seoul 03080, Korea
*
Author to whom correspondence should be addressed.
Received: 9 January 2018 / Revised: 19 March 2018 / Accepted: 5 April 2018 / Published: 6 April 2018
(This article belongs to the Special Issue Marine Oligosaccharides and Polysaccharides)
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Abstract

Mesenchymal stem cells (MSCs) are a source for cell-based therapy. Although MSCs have the potential for tissue regeneration, their therapeutic efficacy is restricted by the uremic toxin, p-cresol, in chronic kidney disease (CKD). To address this issue, we investigated the effect of fucoidan, a marine sulfated polysaccharide, on cellular senescence in MSCs. After p-cresol exposure, MSC senescence was induced, as indicated by an increase in cell size and a decrease in proliferation capacity. Treatment of senescent MSCs with fucoidan significantly reversed this cellular senescence via regulation of SMP30 and p21, and increased proliferation through the regulation of cell cycle-associated proteins (CDK2, CDK4, cyclin D1, and cyclin E). These effects were dependent on FAK-Akt-TWIST signal transduction. In particular, fucoidan promoted the expression of cellular prion protein (PrPC), which resulted in the maintenance of cell expansion capacity in p-cresol-induced senescent MSCs. This protective effect of fucoidan on senescence-mediated inhibition of proliferation was dependent on the TWIST-PrPC axis. In summary, this study shows that fucoidan protects against p-cresol-induced cellular senescence in MSCs through activation of the FAK-Akt-TWIST pathway and suggests that fucoidan could be used in conjunction with functional MSC-based therapies in the treatment of CKD. View Full-Text
Keywords: cellular senescence; chronic kidney disease; fucoidan; mesenchymal stem cells; p-cresol cellular senescence; chronic kidney disease; fucoidan; mesenchymal stem cells; p-cresol
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Lee, J.H.; Yun, C.W.; Hur, J.; Lee, S.H. Fucoidan Rescues p-Cresol-Induced Cellular Senescence in Mesenchymal Stem Cells via FAK-Akt-TWIST Axis. Mar. Drugs 2018, 16, 121.

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