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Improved anti-fibrotic effects by combined treatments of simvastatin and NS-398 in experimental liver fibrosis models

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dc.contributor.authorKang, Seong Hee-
dc.contributor.authorYim, Hyung Joon-
dc.contributor.authorHwang, Ji-won-
dc.contributor.authorKim, Mi-jung-
dc.contributor.authorLee, Young-Sun-
dc.contributor.authorJung, Young Kul-
dc.contributor.authorYim, Hyungshin-
dc.contributor.authorKim, Baek-Hui-
dc.contributor.authorPark, Hae-Chul-
dc.contributor.authorSeo, Yeon Seok-
dc.contributor.authorKim, Ji Hoon-
dc.contributor.authorYeon, Jong Eun-
dc.contributor.authorUm, Soon Ho-
dc.contributor.authorByun, Kwan Soo-
dc.date.accessioned2022-07-26T02:40:20Z-
dc.date.available2022-07-26T02:40:20Z-
dc.date.created2022-07-26-
dc.date.issued2022-07-
dc.identifier.issn1226-3303-
dc.identifier.urihttps://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/61212-
dc.description.abstractBackground/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.language영어-
dc.language.isoen-
dc.publisher대한내과학회-
dc.titleImproved anti-fibrotic effects by combined treatments of simvastatin and NS-398 in experimental liver fibrosis models-
dc.typeArticle-
dc.contributor.affiliatedAuthorYim, Hyung Joon-
dc.contributor.affiliatedAuthorLee, Young-Sun-
dc.contributor.affiliatedAuthorJung, Young Kul-
dc.contributor.affiliatedAuthorKim, Baek-Hui-
dc.contributor.affiliatedAuthorPark, Hae-Chul-
dc.contributor.affiliatedAuthorSeo, Yeon Seok-
dc.contributor.affiliatedAuthorKim, Ji Hoon-
dc.contributor.affiliatedAuthorYeon, Jong Eun-
dc.contributor.affiliatedAuthorUm, Soon Ho-
dc.contributor.affiliatedAuthorByun, Kwan Soo-
dc.identifier.doi10.3904/kjim.2021.138-
dc.identifier.scopusid2-s2.0-85134082707-
dc.identifier.wosid000822778300006-
dc.identifier.bibliographicCitationThe Korean Journal of Internal Medicine, v.37, no.4, pp.745 - 756-
dc.relation.isPartOfThe Korean Journal of Internal Medicine-
dc.citation.titleThe Korean Journal of Internal Medicine-
dc.citation.volume37-
dc.citation.number4-
dc.citation.startPage745-
dc.citation.endPage756-
dc.type.rimsART-
dc.type.docTypeArticle-
dc.identifier.kciidART002849289-
dc.description.journalClass1-
dc.description.isOpenAccessY-
dc.description.journalRegisteredClassscie-
dc.description.journalRegisteredClassscopus-
dc.description.journalRegisteredClasskci-
dc.relation.journalResearchAreaGeneral & Internal Medicine-
dc.relation.journalWebOfScienceCategoryMedicine, General & Internal-
dc.subject.keywordPlusGROWTH-FACTOR-BETA-
dc.subject.keywordPlusHEPATIC-FIBROSIS-
dc.subject.keywordPlusINHIBITION-
dc.subject.keywordPlusEXPRESSION-
dc.subject.keywordPlusAPOPTOSIS-
dc.subject.keywordPlusCELLS-
dc.subject.keywordPlusPROLIFERATION-
dc.subject.keywordPlusREVERSIBILITY-
dc.subject.keywordPlusMITOCHONDRIA-
dc.subject.keywordPlusFIBROGENESIS-
dc.subject.keywordAuthorLiver cirrhosis-
dc.subject.keywordAuthorHydroxymethylglutaryl-CoA reductase inhibitors-
dc.subject.keywordAuthorCyclooxygenase 2 inhibitors-
dc.subject.keywordAuthorHepatic stellate cells-
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2. Clinical Science > Department of Pathology > 1. Journal Articles
2. Clinical Science > Department of Gastroenterology and Hepatology > 1. Journal Articles

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Guro Hospital (Department of Gastroenterology and Hepatology, Guro Hospital)
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