Glutathione dynamics determine the therapeutic efficacy of mesenchymal stem cells for graft-versus-host disease via CREB1-NRF2 pathway
DC Field | Value | Language |
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dc.contributor.author | Lim, Jisun | - |
dc.contributor.author | Heo, Jinbeom | - |
dc.contributor.author | Ju, Hyein | - |
dc.contributor.author | Shin, Ji-Woong | - |
dc.contributor.author | Kim, YongHwan | - |
dc.contributor.author | Lee, Seungun | - |
dc.contributor.author | Yu, Hwan Yeul | - |
dc.contributor.author | Ryu, Chae-Min | - |
dc.contributor.author | Yun, HongDuck | - |
dc.contributor.author | Song, Sujin | - |
dc.contributor.author | Hong, Ki-Sung | - |
dc.contributor.author | Chung, Hyung-Min | - |
dc.contributor.author | Kim, Hwa-Ryeon | - |
dc.contributor.author | Roe, Jae-Seok | - |
dc.contributor.author | Choi, Kihang | - |
dc.contributor.author | Kim, In-Gyu | - |
dc.contributor.author | Jeong, Eui Man | - |
dc.contributor.author | Shin, Dong-Myung | - |
dc.date.accessioned | 2021-08-31T04:40:35Z | - |
dc.date.available | 2021-08-31T04:40:35Z | - |
dc.date.created | 2021-06-19 | - |
dc.date.issued | 2020-04 | - |
dc.identifier.issn | 2375-2548 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/56720 | - |
dc.description.abstract | Glutathione (GSH), the most abundant nonprotein thiol functioning as an antioxidant, plays critical roles in maintaining the core functions of mesenchymal stem cells (MSCs), which are used as a cellular immunotherapy for graft-versus-host disease (GVHD). However, the role of GSH dynamics in MSCs remains elusive. Genome-wide gene expression profiling and high-throughput live-cell imaging assays revealed that CREB1 enforced the GSH-recovering capacity (GRC) of MSCs through NRF2 by directly up-regulating NRF2 target genes responsible for GSH synthesis and redox cycling. MSCs with enhanced GSH levels and GRC mediated by CREB1-NRF2 have improved self-renewal, migratory, anti-inflammatory, and T cell suppression capacities. Administration of MSCs overexpressing CREB1-NRF2 target genes alleviated GVHD in a humanized mouse model, resulting in improved survival, decreased weight loss, and reduced histopathologic damages in GVHD target organs. Collectively, these findings demonstrate the molecular and functional importance of the CREB1-NRF2 pathway in maintaining MSC GSH dynamics, determining therapeutic outcomes for GVHD treatment. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | AMER ASSOC ADVANCEMENT SCIENCE | - |
dc.subject | PROTEIN-KINASE-A | - |
dc.subject | STROMAL CELLS | - |
dc.subject | MOUSE | - |
dc.subject | REVEALS | - |
dc.subject | SAFETY | - |
dc.subject | MODEL | - |
dc.subject | RISK | - |
dc.subject | NRF2 | - |
dc.title | Glutathione dynamics determine the therapeutic efficacy of mesenchymal stem cells for graft-versus-host disease via CREB1-NRF2 pathway | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Choi, Kihang | - |
dc.identifier.doi | 10.1126/sciadv.aba1334 | - |
dc.identifier.scopusid | 2-s2.0-85083548397 | - |
dc.identifier.wosid | 000528276800046 | - |
dc.identifier.bibliographicCitation | SCIENCE ADVANCES, v.6, no.16 | - |
dc.relation.isPartOf | SCIENCE ADVANCES | - |
dc.citation.title | SCIENCE ADVANCES | - |
dc.citation.volume | 6 | - |
dc.citation.number | 16 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Science & Technology - Other Topics | - |
dc.relation.journalWebOfScienceCategory | Multidisciplinary Sciences | - |
dc.subject.keywordPlus | PROTEIN-KINASE-A | - |
dc.subject.keywordPlus | STROMAL CELLS | - |
dc.subject.keywordPlus | MOUSE | - |
dc.subject.keywordPlus | REVEALS | - |
dc.subject.keywordPlus | SAFETY | - |
dc.subject.keywordPlus | MODEL | - |
dc.subject.keywordPlus | RISK | - |
dc.subject.keywordPlus | NRF2 | - |
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