Macrophage inhibitory cytokine-1 aggravates diet-induced gallstone formation via increased ABCG5/ABCG8 expression
DC Field | Value | Language |
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dc.contributor.author | Kim, Min Hee | - |
dc.contributor.author | Lee, Eun-Ji | - |
dc.contributor.author | Kim, Su-Jeong | - |
dc.contributor.author | Jung, Yun-Jae | - |
dc.contributor.author | Park, Woo-Jae | - |
dc.contributor.author | Park, Inkeun | - |
dc.date.accessioned | 2023-08-11T02:40:12Z | - |
dc.date.available | 2023-08-11T02:40:12Z | - |
dc.date.issued | 2023-06 | - |
dc.identifier.issn | 1932-6203 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/88719 | - |
dc.description.abstract | Macrophage inhibitory cytokine 1 (MIC-1), which is overproduced in various human cancers and associated with cachexia, acts on the hypothalamus to suppress appetite and reduce body weight. We investigated the mechanisms through which MIC-1 affects bile acid metabolism and gallstone formation, which are poorly understood. Over 6 weeks, male C57BL/6 mice fed either standard chow or a lithogenic diet were intraperitoneally injected with phosphate-buffered saline (PBS) or MIC-1 (200 mu g/kg/week). Among lithogenic diet-fed mice, MIC-1 treatment resulted in increased gallstone formation compared with PBS treatment. Compared with PBS treatment, MIC-1 treatment decreased hepatic cholesterol and bile acid levels and reduced expression of HMG-CoA reductase (HMGCR), the master cholesterol metabolism regulator sterol regulatory element-binding protein 2, cholesterol 7 alpha-hydroxylase (CYP7A1), mitochondrial sterol 27-hydroxylase, and oxysterol 7 alpha-hydroxylase. Compared with PBS treatment, MIC-1 treatment had no effect on small heterodimer partner, farnesoid X receptor, or pregnane X receptor expression, and extracellular signal-related kinase and c-Jun N-terminal kinase phosphorylation decreased, suggesting that these factors do not contribute to the MIC-1-induced reduction in CYP7A1 expression. Compared with PBS treatment, MIC-1 treatment increased AMP-activated protein kinase (AMPK) phosphorylation. Treatment with the AMPK activator 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) reduced CYP7A1 and HMGCR expression, whereas the AMPK inhibitor Compound C reversed MIC-1-induced reductions in CYP7A1 and HMGCR expression. Furthermore, in MIC-1-treated mice, total biliary cholesterol levels increased together with increased ATP-binding cassette subfamily G (ABCG)5 and ABCG8 expression. Compared with PBS treatment, MIC-1 treatment did not affect expression of liver X receptors alpha and beta, liver receptor homolog 1, hepatocyte nuclear factor 4 alpha, or NR1I3 (also known as constitutive androstane receptor), which are upstream of ABCG5/8; however, MIC-1 treatment increased ABCG5/8 expression and promoter activities. Our study indicates that MIC-1 influences gallstone formation by increasing AMPK phosphorylation, reducing CYP7A1 and HMGCR expression, and increasing ABCG5 and ABCG8 expression. | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | PUBLIC LIBRARY SCIENCE | - |
dc.title | Macrophage inhibitory cytokine-1 aggravates diet-induced gallstone formation via increased ABCG5/ABCG8 expression | - |
dc.type | Article | - |
dc.identifier.wosid | 001010596300025 | - |
dc.identifier.doi | 10.1371/journal.pone.0287146 | - |
dc.identifier.bibliographicCitation | PLOS ONE, v.18, no.6 | - |
dc.description.isOpenAccess | Y | - |
dc.identifier.scopusid | 2-s2.0-85161935564 | - |
dc.citation.title | PLOS ONE | - |
dc.citation.volume | 18 | - |
dc.citation.number | 6 | - |
dc.type.docType | Article | - |
dc.publisher.location | 미국 | - |
dc.subject.keywordPlus | STEROL TRANSPORTERS ABCG5 | - |
dc.subject.keywordPlus | HMG-COA REDUCTASE | - |
dc.subject.keywordPlus | X-RECEPTOR-ALPHA | - |
dc.subject.keywordPlus | CHOLESTEROL 7-ALPHA-HYDROXYLASE | - |
dc.subject.keywordPlus | NUCLEAR RECEPTORS | - |
dc.subject.keywordPlus | ACID SYNTHESIS | - |
dc.subject.keywordPlus | BILE-ACIDS | - |
dc.subject.keywordPlus | PATHWAY | - |
dc.subject.keywordPlus | RISK | - |
dc.subject.keywordPlus | TRANSCRIPTION | - |
dc.relation.journalResearchArea | Science & Technology - Other Topics | - |
dc.relation.journalWebOfScienceCategory | Multidisciplinary Sciences | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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