Improved anti-fibrotic effects by combined treat- ments of simvastatin and NS-398 in experimental liver fibrosis models
DC Field | Value | Language |
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dc.contributor.author | Kang, Seong Hee | - |
dc.contributor.author | Yim, Hyung Joon | - |
dc.contributor.author | Hwang, Ji-won | - |
dc.contributor.author | Kim, Mi-jung | - |
dc.contributor.author | Lee, Young-Sun | - |
dc.contributor.author | Jung, Young Kul | - |
dc.contributor.author | Yim, Hyungshin | - |
dc.contributor.author | Kim, Baek-Hui | - |
dc.contributor.author | Park, Hae-Chul | - |
dc.contributor.author | Seo, Yeon Seok | - |
dc.contributor.author | Kim, Ji Hoon | - |
dc.contributor.author | Yeon, Jong Eun | - |
dc.contributor.author | Um, Soon Ho | - |
dc.contributor.author | Byun, Kwan Soo | - |
dc.date.accessioned | 2022-08-10T22:40:30Z | - |
dc.date.available | 2022-08-10T22:40:30Z | - |
dc.date.created | 2022-08-10 | - |
dc.date.issued | 2022-07 | - |
dc.identifier.issn | 1226-3303 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/142786 | - |
dc.description.abstract | Background/Aims: Efficient anti-fibrotic therapies are required for the treatment of liver cirrhosis. Hydroxymethylglu-taryl-coenzyme A reductase inhibitors (statins) and cyclooxygenase-2 (COX-2) inhibitors have been reported to have anti -fi-brotic effects. Here, we investigated whether combined treatment with a statin and a COX-2 inhibitor has synergistic anti -fi-brotic effects. Methods: The effects of treatment strategies incorporating both simvastatin and a COX-2 inhibitor, NS-398, were inves-tigated using an immortalized human hepatic stellate cell line (LX-2) and a hepatic fibrosis mouse model developed using thioacetamide (TAA) in drinking water. Cellular proliferation was investigated via 5-bromo-2-deoxyuridine uptake. Pro-and anti-apoptotic factors were investigated through Western blotting and real-time polymerase chain reaction analysis. Results: The evaluation of the anti-proliferative effects on LX-2 cells showed that the observed effects were more pro-nounced with combination therapy than with single-drug therapy. Moreover, hepatic fibrosis and collagen deposition de-creased significantly in TAA-treated mice in response to the combined treatment strategy. The mechanisms underlying the anti-fibrotic effects of the combination therapy were investigated. The effects of the combination therapy were correlated with increased expression levels of extracellular signal-regulated kinase 1/2 signaling molecules, upregulation of the Bax/Bcl-2 signaling pathway, inhibition of the transforming growth factor-13 signaling pathway, and inhibition of tissue inhibitor of matrix metalloproteinases 1 and 2. Conclusions: The combination of simvastatin and NS-398 resulted in a synergistic anti-fibrotic effect through multiple pathways. These findings offer a theoretical insight into the possible clinical application of this strategy for the treatment of advanced liver diseases with hepatic fibrosis. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | KOREAN ASSOC INTERNAL MEDICINE | - |
dc.subject | GROWTH-FACTOR-BETA | - |
dc.subject | HEPATIC-FIBROSIS | - |
dc.subject | INHIBITION | - |
dc.subject | EXPRESSION | - |
dc.subject | APOPTOSIS | - |
dc.subject | CELLS | - |
dc.subject | PROLIFERATION | - |
dc.subject | REVERSIBILITY | - |
dc.subject | MITOCHONDRIA | - |
dc.subject | FIBROGENESIS | - |
dc.title | Improved anti-fibrotic effects by combined treat- ments of simvastatin and NS-398 in experimental liver fibrosis models | - |
dc.title.alternative | Improved anti-fibrotic effects by combined treatments of simvastatin and NS-398 in experimental liver fibrosis models | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Lee, Young-Sun | - |
dc.identifier.doi | 10.3904/kjim.2021.138 | - |
dc.identifier.scopusid | 2-s2.0-85134082707 | - |
dc.identifier.wosid | 000822778300006 | - |
dc.identifier.bibliographicCitation | KOREAN JOURNAL OF INTERNAL MEDICINE, v.37, no.4, pp.745 - + | - |
dc.relation.isPartOf | KOREAN JOURNAL OF INTERNAL MEDICINE | - |
dc.citation.title | KOREAN JOURNAL OF INTERNAL MEDICINE | - |
dc.citation.volume | 37 | - |
dc.citation.number | 4 | - |
dc.citation.startPage | 745 | - |
dc.citation.endPage | + | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.identifier.kciid | ART002849289 | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | Y | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | General & Internal Medicine | - |
dc.relation.journalWebOfScienceCategory | Medicine, General & Internal | - |
dc.subject.keywordPlus | GROWTH-FACTOR-BETA | - |
dc.subject.keywordPlus | HEPATIC-FIBROSIS | - |
dc.subject.keywordPlus | INHIBITION | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | APOPTOSIS | - |
dc.subject.keywordPlus | CELLS | - |
dc.subject.keywordPlus | PROLIFERATION | - |
dc.subject.keywordPlus | REVERSIBILITY | - |
dc.subject.keywordPlus | MITOCHONDRIA | - |
dc.subject.keywordPlus | FIBROGENESIS | - |
dc.subject.keywordAuthor | Liver cirrhosis | - |
dc.subject.keywordAuthor | Hydroxymethylglutaryl-CoA reductase inhibitors | - |
dc.subject.keywordAuthor | Cyclooxygenase 2 inhibitors | - |
dc.subject.keywordAuthor | Hepatic stellate cells | - |
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