Hepcidin inhibits Smad3 phosphorylation in hepatic stellate cells by impeding ferroportin-mediated regulation of Akt
DC Field | Value | Language |
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dc.contributor.author | Han, Chang Yeob | - |
dc.contributor.author | Koo, Ja Hyun | - |
dc.contributor.author | Kim, Sung Hoon | - |
dc.contributor.author | Gardenghi, Sara | - |
dc.contributor.author | Rivella, Stefano | - |
dc.contributor.author | Strnad, Pavel | - |
dc.contributor.author | Hwang, Se Jin | - |
dc.contributor.author | Kim, Sang Geon | - |
dc.date.accessioned | 2022-07-15T02:47:27Z | - |
dc.date.available | 2022-07-15T02:47:27Z | - |
dc.date.created | 2021-05-12 | - |
dc.date.issued | 2016-12 | - |
dc.identifier.issn | 2041-1723 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/153479 | - |
dc.description.abstract | Hepatic stellate cell (HSC) activation on liver injury facilitates fibrosis. Hepatokines affecting HSCs are largely unknown. Here we show that hepcidin inhibits HSC activation and ameliorates liver fibrosis. We observe that hepcidin levels are inversely correlated with exacerbation of fibrosis in patients, and also confirm the relationship in animal models. Adenoviral delivery of hepcidin to mice attenuates liver fibrosis induced by CCl4 treatment or bile duct ligation. In cell-based assays, either hepcidin from hepatocytes or exogenous hepcidin suppresses HSC activation by inhibiting TGF beta 1-mediated Smad3 phosphorylation via Akt. In activated HSCs, ferroportin is upregulated, which can be prevented by hepcidin treatment. Similarly, ferroportin knockdown in HSCs prohibits TGF beta 1-inducible Smad3 phosphorylation and increases Akt phosphorylation, whereas ferroportin over-expression has the opposite effect. HSC-specific ferroportin deletion also ameliorates liver fibrosis. In summary, hepcidin suppresses liver fibrosis by impeding TGF beta 1-induced Smad3 phosphorylation in HSCs, which depends on Akt activated by a deficiency of ferroportin. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | Nature Publishing Group | - |
dc.title | Hepcidin inhibits Smad3 phosphorylation in hepatic stellate cells by impeding ferroportin-mediated regulation of Akt | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Hwang, Se Jin | - |
dc.identifier.doi | 10.1038/ncomms13817 | - |
dc.identifier.scopusid | 2-s2.0-85006999095 | - |
dc.identifier.wosid | 000390261600001 | - |
dc.identifier.bibliographicCitation | Nature Communications, v.7, pp.1 - 14 | - |
dc.relation.isPartOf | Nature Communications | - |
dc.citation.title | Nature Communications | - |
dc.citation.volume | 7 | - |
dc.citation.startPage | 1 | - |
dc.citation.endPage | 14 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | Y | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Science & Technology - Other Topics | - |
dc.relation.journalWebOfScienceCategory | Multidisciplinary Sciences | - |
dc.subject.keywordPlus | LIVER FIBROSIS | - |
dc.subject.keywordPlus | IRON-OVERLOAD | - |
dc.subject.keywordPlus | TGF-BETA | - |
dc.subject.keywordPlus | HEPATOCELLULAR-CARCINOMA | - |
dc.subject.keywordPlus | THERAPEUTIC TARGET | - |
dc.subject.keywordPlus | MICE | - |
dc.subject.keywordPlus | MACROPHAGES | - |
dc.subject.keywordPlus | INJURY | - |
dc.subject.keywordPlus | HEPATOCYTES | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.identifier.url | https://www.nature.com/articles/ncomms13817 | - |
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