Exogenous 8-hydroxydeoxyguanosine ameliorates liver fibrosis through the inhibition of Rac1-NADPH oxidase signaling
DC Field | Value | Language |
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dc.contributor.author | Shin, Seung Kak | - |
dc.contributor.author | Kim, Kyung-Ok | - |
dc.contributor.author | Kim, Se-Hee | - |
dc.contributor.author | Kwon, Oh Sang | - |
dc.contributor.author | Choi, Cheol Soo | - |
dc.contributor.author | Jeong, Sung Hwan | - |
dc.contributor.author | Kim, Yun Soo | - |
dc.contributor.author | Kim, Ju Hyun | - |
dc.contributor.author | Chung, Myung-Hee | - |
dc.date.available | 2020-03-03T06:47:37Z | - |
dc.date.created | 2020-02-24 | - |
dc.date.issued | 2020-06 | - |
dc.identifier.issn | 0815-9319 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/17827 | - |
dc.description.abstract | Background and Aim Exogenous 8-hydroxydeoxyguanosine (8-OHdG) was suggested as an inhibitor of Rac1 and NADPH oxidase (NOX). The aim of this study was to evaluate the effects of the exogenous 8-OHdG on hepatic fibrogenesis in vitro and in vivo model of liver fibrosis. Methods Adult Sprague-Dawley rats were allocated to sham-operated rats (n = 7), rats that underwent bile duct ligation (BDL) (n = 6), and BDL rats treated with 8-OHdG (60 mg/kg/day by gavage, n = 6). All rats were sacrificed on day 21. Double immunofluorescence staining between either NOX1 or NOX2 and alpha-smooth muscle actin (SMA) in liver was performed. Hepatic fibrotic contents were assessed by hydroxyproline assay and quantified by Sirius red staining. In vitro, hepatic stellate cell (HSC) line LX-2 and HHSteC cells were stimulated by angiotensin II (10 mu M). The reactive oxygen species (ROS) production was measured by confocal microscopy. The expressions of NOX1, NOX2, alpha-SMA, transforming growth factor (TGF)-beta 1, and collagen I alpha were analyzed by quantitative real-time polymerase chain reaction or immunoblotting. Results The 8-OHdG treatment in BDL rats reduced the NOX1 and NOX2 protein expression, which overlapped with alpha-SMA compared with BDL rats. The 8-OHdG treatment in BDL rats significantly decreased the mRNA expression of NOX1, NOX2, alpha-SMA, TGF-beta 1, and collagen I alpha, and fibrotic contents. Increases of ROS production, Rac1 activation, NOX1, NOX2, and fibronectin expression induced by angiotensin II in HSCs were attenuated by 8-OHdG. Conclusions Rac1 activation and NOX-derived ROS are implicated to liver fibrosis. The 8-OHdG ameliorates liver fibrosis through the inhibition of Rac1 activation and NOX-derived ROS. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | WILEY | - |
dc.relation.isPartOf | JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY | - |
dc.title | Exogenous 8-hydroxydeoxyguanosine ameliorates liver fibrosis through the inhibition of Rac1-NADPH oxidase signaling | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000508764400001 | - |
dc.identifier.doi | 10.1111/jgh.14979 | - |
dc.identifier.bibliographicCitation | JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY | - |
dc.description.isOpenAccess | N | - |
dc.identifier.scopusid | 2-s2.0-85078768903 | - |
dc.citation.title | JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY | - |
dc.contributor.affiliatedAuthor | Shin, Seung Kak | - |
dc.contributor.affiliatedAuthor | Kim, Kyung-Ok | - |
dc.contributor.affiliatedAuthor | Kim, Se-Hee | - |
dc.contributor.affiliatedAuthor | Kwon, Oh Sang | - |
dc.contributor.affiliatedAuthor | Choi, Cheol Soo | - |
dc.contributor.affiliatedAuthor | Jeong, Sung Hwan | - |
dc.contributor.affiliatedAuthor | Kim, Yun Soo | - |
dc.contributor.affiliatedAuthor | Kim, Ju Hyun | - |
dc.contributor.affiliatedAuthor | Chung, Myung-Hee | - |
dc.type.docType | Article; Early Access | - |
dc.subject.keywordAuthor | 8-hydroxydeoxyguanosine | - |
dc.subject.keywordAuthor | Liver fibrosis | - |
dc.subject.keywordAuthor | NADPH oxidase | - |
dc.subject.keywordAuthor | Rac1 | - |
dc.subject.keywordPlus | HEPATIC STELLATE CELLS | - |
dc.subject.keywordPlus | OXIDATIVE STRESS | - |
dc.subject.keywordPlus | ANGIOTENSIN-II | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | DNA | - |
dc.subject.keywordPlus | APOPTOSIS | - |
dc.subject.keywordPlus | DAMAGE | - |
dc.subject.keywordPlus | RAC1 | - |
dc.relation.journalResearchArea | Gastroenterology & Hepatology | - |
dc.relation.journalWebOfScienceCategory | Gastroenterology & Hepatology | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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