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The oxidative phosphorylation inhibitor IM156 suppresses B-cell activation by regulating mitochondrial membrane potential and contributes to the mitigation of systemic lupus erythematosus
DC Field | Value | Language |
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dc.contributor.author | 김범석 | - |
dc.contributor.author | 송정식 | - |
dc.contributor.author | 임범진 | - |
dc.contributor.author | 정재호 | - |
dc.date.accessioned | 2024-01-16T01:54:29Z | - |
dc.date.available | 2024-01-16T01:54:29Z | - |
dc.date.issued | 2023-02 | - |
dc.identifier.issn | 0085-2538 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/197786 | - |
dc.description.abstract | Current treatment strategies for autoimmune diseases may not sufficiently control aberrant metabolism in B-cells. To address this concern, we investigated a biguanide derivative, IM156, as a potential regulator for B-cell metabolism in vitro and in vivo on overactive B-cells stimulated by the pro-inflammatory receptor TLR-9 agonist CpG oligodeoxynucleotide, a mimic of viral/bacterial DNA. Using RNA sequencing, we analyzed the B-cell transcriptome expression, identifying the major molecular pathways affected by IM156 in vivo. We also evaluated the anti-inflammatory effects of IM156 in lupus-prone NZB/W F1 mice. CD19+B-cells exhibited higher mitochondrial mass and mitochondrial membrane potential compared to T-cells and were more susceptible to IM156-mediated oxidative phosphorylation inhibition. In vivo, IM156 inhibited mitochondrial oxidative phosphorylation, cell cycle progression, plasmablast differentiation, and activation marker levels in CpG oligodeoxynucleotide-stimulated mouse spleen B-cells. Interestingly, IM156 treatment significantly increased overall survival, reduced glomerulonephritis and inhibited B-cell activation in the NZB/W F1 mice. Thus, our data indicated that IM156 suppressed the mitochondrial membrane potentials of activated B-cells in mice, contributing to the mitigation of lupus activity. Hence, IM156 may represent a therapeutic alternative for autoimmune disease mediated by B-cell hyperactivity. | - |
dc.description.statementOfResponsibility | restriction | - |
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 | Autoimmune Diseases* | - |
dc.subject.MESH | B-Lymphocytes | - |
dc.subject.MESH | Lupus Erythematosus, Systemic* / drug therapy | - |
dc.subject.MESH | Membrane Potential, Mitochondrial | - |
dc.subject.MESH | Mice | - |
dc.subject.MESH | Mice, Inbred NZB | - |
dc.subject.MESH | Oligodeoxyribonucleotides / pharmacology | - |
dc.subject.MESH | Oxidative Phosphorylation | - |
dc.title | The oxidative phosphorylation inhibitor IM156 suppresses B-cell activation by regulating mitochondrial membrane potential and contributes to the mitigation of systemic lupus erythematosus | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학교실) | - |
dc.contributor.googleauthor | Joo Sung Shim | - |
dc.contributor.googleauthor | Eun Jee Kim | - |
dc.contributor.googleauthor | Lucy Eunju Lee | - |
dc.contributor.googleauthor | Joon Ye Kim | - |
dc.contributor.googleauthor | Yuri Cho | - |
dc.contributor.googleauthor | Hanna Kim | - |
dc.contributor.googleauthor | Jieun Kim | - |
dc.contributor.googleauthor | Sung Hoon Jang | - |
dc.contributor.googleauthor | Jimin Son | - |
dc.contributor.googleauthor | Jae-Ho Cheong | - |
dc.contributor.googleauthor | Aekyong Kim | - |
dc.contributor.googleauthor | Beom Jin Lim | - |
dc.contributor.googleauthor | Sang-Jun Ha | - |
dc.contributor.googleauthor | Jason Jungsik Song | - |
dc.contributor.googleauthor | Beom Seok Kim | - |
dc.identifier.doi | 10.1016/j.kint.2022.09.031. | - |
dc.contributor.localId | A00488 | - |
dc.contributor.localId | A02057 | - |
dc.contributor.localId | A03363 | - |
dc.contributor.localId | A03717 | - |
dc.relation.journalcode | J01941 | - |
dc.identifier.eissn | 1523-1755 | - |
dc.identifier.pmid | 36332729 | - |
dc.identifier.url | https://www.sciencedirect.com/science/article/pii/S0085253822009139 | - |
dc.subject.keyword | B-cell metabolism | - |
dc.subject.keyword | IM156 | - |
dc.subject.keyword | autoimmune diseases | - |
dc.subject.keyword | systemic lupus erythematosus | - |
dc.contributor.alternativeName | Kim, Beom Seok | - |
dc.contributor.affiliatedAuthor | 김범석 | - |
dc.contributor.affiliatedAuthor | 송정식 | - |
dc.contributor.affiliatedAuthor | 임범진 | - |
dc.contributor.affiliatedAuthor | 정재호 | - |
dc.citation.volume | 103 | - |
dc.citation.number | 2 | - |
dc.citation.startPage | 343 | - |
dc.citation.endPage | 356 | - |
dc.identifier.bibliographicCitation | KIDNEY INTERNATIONAL, Vol.103(2) : 343-356, 2023-02 | - |
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