{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T05:42:23Z","timestamp":1790055743085,"version":"4.0.1"},"reference-count":29,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2018,4,6]],"date-time":"2018-04-06T00:00:00Z","timestamp":1522972800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/md16040121","type":"journal-article","created":{"date-parts":[[2018,4,10]],"date-time":"2018-04-10T13:06:08Z","timestamp":1523365568000},"page":"121","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Fucoidan Rescues p-Cresol-Induced Cellular Senescence in Mesenchymal Stem Cells via FAK-Akt-TWIST Axis"],"prefix":"10.3390","volume":"16","author":[{"given":"Jun","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Alabama at Birmingham School of Medicine, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chul","family":"Yun","sequence":"additional","affiliation":[{"name":"Medical Science Research Institute, Soonchunhyang University Seoul Hospital, Seoul 04401, Korea"},{"name":"Departments of Biochemistry, Soonchunhyang University College of Medicine, Cheonan 330-930, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Hur","sequence":"additional","affiliation":[{"name":"Center for Medical Innovation, Seoul National University Hospital, Seoul 03080, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6713-8229","authenticated-orcid":false,"given":"Sang","family":"Lee","sequence":"additional","affiliation":[{"name":"Medical Science Research Institute, Soonchunhyang University Seoul Hospital, Seoul 04401, Korea"},{"name":"Departments of Biochemistry, Soonchunhyang University College of Medicine, Cheonan 330-930, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,4,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1002\/stem.1681","article-title":"Concise review: The surface markers and identity of human mesenchymal stem cells","volume":"32","author":"Lv","year":"2014","journal-title":"Stem Cells"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2739","DOI":"10.1634\/stemcells.2007-0197","article-title":"Concise review: Mesenchymal stem cells: Their phenotype, differentiation capacity, immunological features, and potential for homing","volume":"25","author":"Chamberlain","year":"2007","journal-title":"Stem Cells"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.stem.2011.06.008","article-title":"The MSC: An injury drugstore","volume":"9","author":"Caplan","year":"2011","journal-title":"Cell Stem Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4798639","DOI":"10.1155\/2016\/4798639","article-title":"Mesenchymal stem cell-based therapy for kidney disease: A review of clinical evidence","volume":"2016","author":"Peired","year":"2016","journal-title":"Stem Cells Int."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.2215\/CJN.07971109","article-title":"p-Cresol and cardiovascular risk in mild-to-moderate kidney disease","volume":"5","author":"Meijers","year":"2010","journal-title":"Clin. 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