{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T03:01:36Z","timestamp":1790564496380,"version":"4.1.0"},"reference-count":48,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2018,1,25]],"date-time":"2018-01-25T00:00:00Z","timestamp":1516838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation grant funded by the Korean government","award":["2016R1D1A3B01007727"],"award-info":[{"award-number":["2016R1D1A3B01007727"]}]},{"name":"National Research Foundation grant funded by the Korean government","award":["2017M3A9B4032528"],"award-info":[{"award-number":["2017M3A9B4032528"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mesenchymal stem cells (MSCs) could be a promising solution in the treatment of various diseases including chronic kidney disease (CKD). However, endoplasmic reticulum (ER) stress induced by ischemia in the area of application limits the integration and survival of MSCs in patients. In our study, we generated ER stress-induced conditions in MSCs using P-cresol. As P-cresol is a toxic compound accumulated in the body of CKD patients and induces apoptosis and inflammation through reactive oxygen species (ROS), we observed ER stress-induced MSC apoptosis activated by oxidative stress, which in turn resulted from ROS generation. To overcome stress-induced apoptosis, we investigated the protective effects of tauroursodeoxycholic acid (TUDCA), a bile acid, on ER stress in MSCs. In ER stress, TUDCA treatment of MSCs reduced ER stress-associated protein activation, including GRP78, PERK, eIF2\u03b1, ATF4, IRE1\u03b1, and CHOP. Next, to explore the protective mechanism adopted by TUDCA, TUDCA-mediated cellular prion protein (PrPC) activation was assessed. We confirmed that PrPC expression significantly increased ROS, which was eliminated by superoxide dismutase and catalase in MSCs. These findings suggest that TUDCA protects from inflammation and apoptosis in ER stress via PrPC expression. Our study demonstrates that TUDCA protects MSCs against inflammation and apoptosis in ER stress by PrPC expression in response to P-cresol exposure.<\/jats:p>","DOI":"10.3390\/ijms19020352","type":"journal-article","created":{"date-parts":[[2018,1,25]],"date-time":"2018-01-25T12:25:49Z","timestamp":1516883149000},"page":"352","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Tauroursodeoxycholic Acid Protects against the Effects of P-Cresol-Induced Reactive Oxygen Species via the Expression of Cellular Prion Protein"],"prefix":"10.3390","volume":"19","author":[{"given":"Seung","family":"Yun","sequence":"first","affiliation":[{"name":"Department of Neurology, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeo","family":"Yoon","sequence":"additional","affiliation":[{"name":"Institute of Soonchunhyang Medical Science Research, Soonchunhyang University Hospital Seoul, Soonchunhyang University, Seoul 04401, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Lee","sequence":"additional","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":"Minjee","family":"Kook","sequence":"additional","affiliation":[{"name":"Department of Neurology, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Seok","family":"Han","sequence":"additional","affiliation":[{"name":"Institute of Soonchunhyang Medical Science Research, Soonchunhyang University Hospital Seoul, Soonchunhyang University, Seoul 04401, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seo","family":"Jung","sequence":"additional","affiliation":[{"name":"Institute of Soonchunhyang Medical Science Research, Soonchunhyang University Hospital Seoul, Soonchunhyang University, Seoul 04401, 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":"Institute of Soonchunhyang Medical Science Research, Soonchunhyang University Hospital Seoul, Soonchunhyang University, Seoul 04401, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,1,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1764","DOI":"10.1046\/j.1523-1755.2003.00912.x","article-title":"Involvement of voltage- and ligand-gated Ca2+ channels in the neuroexcitatory and synergistic effects of putative uremic neurotoxins","volume":"63","author":"Marescau","year":"2003","journal-title":"Kidney Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1056\/NEJMoa041031","article-title":"Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization","volume":"351","author":"Go","year":"2004","journal-title":"N. 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