DC Field | Value | Language |
---|---|---|
dc.contributor.author | Jin, Hye Jin | ko |
dc.contributor.author | Lee, Hyang Ju | ko |
dc.contributor.author | Heo, Jinbeom | ko |
dc.contributor.author | Lim, Jisun | ko |
dc.contributor.author | Kim, Miyeon | ko |
dc.contributor.author | Kim, Min Kyung | ko |
dc.contributor.author | Nam, Hae Yun | ko |
dc.contributor.author | Hong, Gyong Hwa | ko |
dc.contributor.author | Cho, You Sook | ko |
dc.contributor.author | Choi, Soo Jin | ko |
dc.contributor.author | Kim, In-Gyu | ko |
dc.contributor.author | Shin, Dong-Myung | ko |
dc.contributor.author | Kim, Seong Who | ko |
dc.date.accessioned | 2016-07-04T01:56:34Z | - |
dc.date.available | 2016-07-04T01:56:34Z | - |
dc.date.created | 2016-04-27 | - |
dc.date.created | 2016-04-27 | - |
dc.date.issued | 2016-03 | - |
dc.identifier.citation | ANTIOXIDANTS & REDOX SIGNALING, v.24, no.9, pp.471 - 485 | - |
dc.identifier.issn | 1523-0864 | - |
dc.identifier.uri | http://hdl.handle.net/10203/208763 | - |
dc.description.abstract | Aims: Cellular senescence and its secretory phenotype (senescence-associated secretory phenotype [SASP]) develop after long-term expansion of mesenchymal stromal cells (MSCs). Further investigation of this phenotype is required to improve the therapeutic efficacy of MSC-based cell therapies. In this study, we show that positive feedback between SASP and inherent senescence processes plays a crucial role in the senescence of umbilical cord blood-derived MSCs (UCB-MSCs). Results: We found that monocyte chemoattractant protein-1 (MCP-1) was secreted as a dominant component of the SASP during expansion of UCB-MSCs and reinforced senescence via its cognate receptor chemokine (c-c motif) receptor 2 (CCR2) by activating the ROS-p38-MAPK-p53/p21 signaling cascade in both an autocrine and paracrine manner. The activated p53 in turn increased MCP-1 secretion, completing a feed-forward loop that triggered the senescence program in UCB-MSCs. Accordingly, knockdown of CCR2 in UCB-MSCs significantly improved their therapeutic ability to alleviate airway inflammation in an experimental allergic asthma model. Moreover, BMI1, a polycomb protein, repressed the expression of MCP-1 by binding to its regulatory elements. The reduction in BMI1 levels during UCB-MSC senescence altered the epigenetic status of MCP-1, including the loss of H2AK119Ub, and resulted in derepression of MCP-1. Innovation: Our results provide the first evidence supporting the existence of the SASP as a causative contributor to UCB-MSC senescence and reveal a so far unappreciated link between epigenetic regulation and SASP for maintaining a stable senescent phenotype. Conclusion: Senescence of UCB-MSCs is orchestrated by MCP-1, which is secreted as a major component of the SASP and is epigenetically regulated by BMI1. Antioxid. Redox Signal. 24, 471-485 | - |
dc.language | English | - |
dc.publisher | MARY ANN LIEBERT INC | - |
dc.subject | UMBILICAL-CORD BLOOD | - |
dc.subject | HEMATOPOIETIC STEM-CELLS | - |
dc.subject | CELLULAR SENESCENCE | - |
dc.subject | PROTEIN-1 RECEPTOR | - |
dc.subject | SELF-RENEWAL | - |
dc.subject | BIOLOGY | - |
dc.subject | AGE | - |
dc.subject | INFLAMMATION | - |
dc.subject | PHENOTYPE | - |
dc.subject | DISEASE | - |
dc.title | Senescence-Associated MCP-1 Secretion Is Dependent on a Decline in BMI1 in Human Mesenchymal Stromal Cells | - |
dc.type | Article | - |
dc.identifier.wosid | 000372849500001 | - |
dc.identifier.scopusid | 2-s2.0-84962022981 | - |
dc.type.rims | ART | - |
dc.citation.volume | 24 | - |
dc.citation.issue | 9 | - |
dc.citation.beginningpage | 471 | - |
dc.citation.endingpage | 485 | - |
dc.citation.publicationname | ANTIOXIDANTS & REDOX SIGNALING | - |
dc.identifier.doi | 10.1089/ars.2015.6359 | - |
dc.contributor.nonIdAuthor | Jin, Hye Jin | - |
dc.contributor.nonIdAuthor | Lee, Hyang Ju | - |
dc.contributor.nonIdAuthor | Heo, Jinbeom | - |
dc.contributor.nonIdAuthor | Lim, Jisun | - |
dc.contributor.nonIdAuthor | Kim, Miyeon | - |
dc.contributor.nonIdAuthor | Kim, Min Kyung | - |
dc.contributor.nonIdAuthor | Nam, Hae Yun | - |
dc.contributor.nonIdAuthor | Cho, You Sook | - |
dc.contributor.nonIdAuthor | Choi, Soo Jin | - |
dc.contributor.nonIdAuthor | Kim, In-Gyu | - |
dc.contributor.nonIdAuthor | Shin, Dong-Myung | - |
dc.contributor.nonIdAuthor | Kim, Seong Who | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | UMBILICAL-CORD BLOOD | - |
dc.subject.keywordPlus | HEMATOPOIETIC STEM-CELLS | - |
dc.subject.keywordPlus | CELLULAR SENESCENCE | - |
dc.subject.keywordPlus | PROTEIN-1 RECEPTOR | - |
dc.subject.keywordPlus | SELF-RENEWAL | - |
dc.subject.keywordPlus | BIOLOGY | - |
dc.subject.keywordPlus | AGE | - |
dc.subject.keywordPlus | INFLAMMATION | - |
dc.subject.keywordPlus | PHENOTYPE | - |
dc.subject.keywordPlus | DISEASE | - |
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