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Retinol from hepatic stellate cells via STRA6 induces lipogenesis on hepatocytes during fibrosis

DC Field Value Language
dc.contributor.authorHwang, Injoo-
dc.contributor.authorLee, Eun Ju-
dc.contributor.authorPark, Hyomin-
dc.contributor.authorMoon, Dodam-
dc.contributor.authorKim, Hyo-Soo-
dc.date.accessioned2021-03-15T05:14:13Z-
dc.date.available2021-03-15T05:14:13Z-
dc.date.issued2021-01-06-
dc.identifier.citationCell & Bioscience. 2021 Jan 06;11(1):3ko_KR
dc.identifier.issn2045-3701-
dc.identifier.urihttps://hdl.handle.net/10371/173589-
dc.description.abstractBackground
Hepatic stellate cells (HSCs) are activated in response to liver injury with TIF1γ-suppression, leading to liver fibrosis. Here, we examined the mechanism how reduction of TIF1γ in HSCs induces damage on hepatocytes and liver fibrosis.

Method
Lrat:Cas9-ERT2:sgTif1γ mice were treated Tamoxifen (TMX) or wild-type mice were treated Thioacetamide (TAA). HSCs were isolated from mice liver and analyzed role of Tif1γ. HepG2 were treated retinol with/without siRNA for Stimulated by retinoic acid 6 (STRA6) or Retinoic acid receptor(RAR)-antagonist, and LX2 were treated siTIF1γ and/or siSTRA6. TAA treated mice were used for evaluation of siSTRA6 effect in liver fibrosis.

Results
When we blocked the Tif1γ in HSCs using Lrat:Cas9-ERT2:sgTif1γ mice, retinol is distributed into hepatocytes. Retinol influx was confirmed using HepG2, and the increased intracellular retinol led to the upregulation of lipogenesis-related-genes and triglyceride. This effect was inhibited by a RAR-antagonist or knock-down of STRA6. In the LX2, TIF1γ-suppression resulted in upregulation of STRA6 and retinol release, which was inhibited by STRA6 knock-down. The role of STRA6-mediated retinol transfer from HSCs to hepatocytes in liver fibrosis was demonstrated by in vivo experiments where blocking of STRA6 reduced fibrosis.

Conclusions
Retinol from HSCs via STRA6 in response to injury with TIF1γ-reduction is taken up by hepatocytes via STRA6, leading to fat-deposition and damage, and liver fibrosis.
ko_KR
dc.description.sponsorshipThis study was supported by a grant of the Korea Health Technology R&D Project Strategic Center of Cell and Bio Therapy (grant number: HI17C2085) and Korea Research-Driven Hospital (grant number: HI14C1277) through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare (MHW), Republic of Korea. The funders had no role in the
study design, data collection and analysis, decision to publish, or preparation of the manuscript.
ko_KR
dc.language.isoenko_KR
dc.publisherBMCko_KR
dc.subjectRetinol-
dc.subjectHepatocytes-
dc.subjectStimulated by retinoic acid 6 (STRA6)-
dc.subjectLipogenesis-
dc.subjectLiver fbrosis-
dc.titleRetinol from hepatic stellate cells via STRA6 induces lipogenesis on hepatocytes during fibrosisko_KR
dc.typeArticleko_KR
dc.contributor.AlternativeAuthor황인주-
dc.contributor.AlternativeAuthor이은주-
dc.contributor.AlternativeAuthor박효민-
dc.contributor.AlternativeAuthor문도담-
dc.contributor.AlternativeAuthor김효수-
dc.identifier.doi10.1186/s13578-020-00509-w-
dc.citation.journaltitleCell & Bioscience.ko_KR
dc.language.rfc3066en-
dc.rights.holderThe Author(s)-
dc.date.updated2021-01-27T10:41:35Z-
dc.citation.number1ko_KR
dc.citation.startpage3ko_KR
dc.citation.volume11ko_KR
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