Improved anti-fibrotic effects by combined treatments of simvastatin and NS-398 in experimental liver fibrosis models
DC Field | Value | Language |
---|---|---|
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 | 2022-07-26T02:40:20Z | - |
dc.date.available | 2022-07-26T02:40:20Z | - |
dc.date.issued | 2022-07 | - |
dc.identifier.issn | 1226-3303 | - |
dc.identifier.issn | 2005-6648 | - |
dc.identifier.uri | https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/61212 | - |
dc.description.abstract | Background/Aims Efficient anti-fibrotic therapies are required for the treatment of liver cirrhosis. Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) and cyclooxygenase-2 (COX-2) inhibitors have been reported to have anti-fibrotic effects. Here, we investigated whether combined treatment with a statin and a COX-2 inhibitor has synergistic anti-fibrotic effects. Methods The effects of treatment strategies incorporating both simvastatin and a COX-2 inhibitor, NS-398, were investigated 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 pronounced with combination therapy than with single-drug therapy. Moreover, hepatic fibrosis and collagen deposition decreased 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-β 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.format.extent | 12 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | 대한내과학회 | - |
dc.title | Improved anti-fibrotic effects by combined treatments of simvastatin and NS-398 in experimental liver fibrosis models | - |
dc.type | Article | - |
dc.publisher.location | 대한민국 | - |
dc.identifier.doi | 10.3904/kjim.2021.138 | - |
dc.identifier.scopusid | 2-s2.0-85134082707 | - |
dc.identifier.wosid | 000822778300006 | - |
dc.identifier.bibliographicCitation | The Korean Journal of Internal Medicine, v.37, no.4, pp 745 - 756 | - |
dc.citation.title | The Korean Journal of Internal Medicine | - |
dc.citation.volume | 37 | - |
dc.citation.number | 4 | - |
dc.citation.startPage | 745 | - |
dc.citation.endPage | 756 | - |
dc.type.docType | Article | - |
dc.identifier.kciid | ART002849289 | - |
dc.description.isOpenAccess | Y | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.description.journalRegisteredClass | kci | - |
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 | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
73, Goryeodae-ro, Seongbuk-gu, Seoul, Republic of Korea (02841)82-2-2286-1265
COPYRIGHT 2020 KOREA UNIVERSITY MEDICAL LIBRARY ALL RIGHTS RESERVED.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.