Cited 8 times in
Macrophage transcription factor TonEBP promotes systemic lupus erythematosus and kidney injury via damage-induced signaling pathways
DC Field | Value | Language |
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dc.contributor.author | 양재석 | - |
dc.contributor.author | 임범진 | - |
dc.date.accessioned | 2023-08-09T06:51:45Z | - |
dc.date.available | 2023-08-09T06:51:45Z | - |
dc.date.issued | 2023-07 | - |
dc.identifier.issn | 0085-2538 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/195985 | - |
dc.description.abstract | Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by autoreactive B cells and dysregulation of many other types of immune cells including myeloid cells. Lupus nephritis (LN) is a common target organ manifestations of SLE. Tonicity-responsive enhancer-binding protein (TonEBP, also known as nuclear factor of activated T-cells 5 (NFAT5)), was initially identified as a central regulator of cellular responses to hypertonic stress and is a pleiotropic stress protein involved in a variety of immunometabolic diseases. To explore the role of TonEBP, we examined kidney biopsy samples from patients with LN. Kidney TonEBP expression was found to be elevated in these patients compared to control patients - in both kidney cells and infiltrating immune cells. Kidney TonEBP mRNA was elevated in LN and correlated with mRNAs encoding inflammatory cytokines and the degree of proteinuria. In a pristane-induced SLE model in mice, myeloid TonEBP deficiency blocked the development of SLE and LN. In macrophages, engagement of various toll-like receptors (TLRs) that respond to damage-associated molecular patterns induced TonEBP expression via stimulation of its promoter. Intracellular signaling downstream of the TLRs was dependent on TonEBP. Therefore, TonEBP can act as a transcriptional cofactor for NF-κB, and activated mTOR-IRF3/7 via protein-protein interactions. Additionally, TonEBP-deficient macrophages displayed elevated efferocytosis and animals with myeloid deficiency of TonEBP showed reduced Th1 and Th17 differentiation, consistent with macrophages defective in TLR signaling. Thus, our data show that myeloid TonEBP may be an attractive therapeutic target for SLE and LN. | - |
dc.description.statementOfResponsibility | open | - |
dc.language | English | - |
dc.publisher | Elsevier | - |
dc.relation.isPartOf | KIDNEY INTERNATIONAL | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Kidney | - |
dc.subject.MESH | Lupus Erythematosus, Systemic* | - |
dc.subject.MESH | Lupus Nephritis* | - |
dc.subject.MESH | Macrophages | - |
dc.subject.MESH | Mice | - |
dc.subject.MESH | NFATC Transcription Factors | - |
dc.subject.MESH | Signal Transduction | - |
dc.title | Macrophage transcription factor TonEBP promotes systemic lupus erythematosus and kidney injury via damage-induced signaling pathways | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학교실) | - |
dc.contributor.googleauthor | Eun Jin Yoo | - |
dc.contributor.googleauthor | Kook-Hwan Oh | - |
dc.contributor.googleauthor | Honglin Piao | - |
dc.contributor.googleauthor | Hyun Je Kang | - |
dc.contributor.googleauthor | Gyu Won Jeong | - |
dc.contributor.googleauthor | Hyun Park | - |
dc.contributor.googleauthor | Chang Jun Lee | - |
dc.contributor.googleauthor | Hyunjin Ryu | - |
dc.contributor.googleauthor | Seung Hee Yang | - |
dc.contributor.googleauthor | Myung-Gyu Kim | - |
dc.contributor.googleauthor | Dong Ki Kim | - |
dc.contributor.googleauthor | Sung Ho Park | - |
dc.contributor.googleauthor | Beom Jin Lim | - |
dc.contributor.googleauthor | Sang Min Lee | - |
dc.contributor.googleauthor | Chan Young Park | - |
dc.contributor.googleauthor | Soo Youn Choi | - |
dc.contributor.googleauthor | Whaseon Lee-Kwon | - |
dc.contributor.googleauthor | Jaeseok Yang | - |
dc.contributor.googleauthor | Hyug Moo Kwon | - |
dc.identifier.doi | 10.1016/j.kint.2023.03.030 | - |
dc.contributor.localId | A06130 | - |
dc.contributor.localId | A03363 | - |
dc.relation.journalcode | J01941 | - |
dc.identifier.eissn | 1523-1755 | - |
dc.identifier.pmid | 37088425 | - |
dc.subject.keyword | glomerulonephritis | - |
dc.subject.keyword | inflammation | - |
dc.subject.keyword | lupus | - |
dc.subject.keyword | macrophages | - |
dc.subject.keyword | systemic lupus erythematosus | - |
dc.contributor.alternativeName | Yang, Jaeseok | - |
dc.contributor.affiliatedAuthor | 양재석 | - |
dc.contributor.affiliatedAuthor | 임범진 | - |
dc.citation.volume | 104 | - |
dc.citation.number | 1 | - |
dc.citation.startPage | 163 | - |
dc.citation.endPage | 180 | - |
dc.identifier.bibliographicCitation | KIDNEY INTERNATIONAL, Vol.104(1) : 163-180, 2023-07 | - |
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