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dc.titleFunctional interaction between macrophages and hepatocytes dictate the outcome of liver fibrosis
dc.contributor.authorXie, Min
dc.contributor.authorChia, Ren Hui
dc.contributor.authorLi, Dan
dc.contributor.authorTeo, Fanny Xueting
dc.contributor.authorKrueger, Christian
dc.contributor.authorSabapathy, Kanaga
dc.identifier.citationXie, Min, Chia, Ren Hui, Li, Dan, Teo, Fanny Xueting, Krueger, Christian, Sabapathy, Kanaga (2021-01-29). Functional interaction between macrophages and hepatocytes dictate the outcome of liver fibrosis. Life Science Alliance 4 (4) : e202000803. ScholarBank@NUS Repository.
dc.description.abstractHepatocytes and liver-resident macrophages known as Kupffer cells (KCs) are key cell types involved in liver fibrosis. The transcription factor c-Jun plays a fundamental role in regulating hepatocyte and macrophage functions. We have examined c-Jun’s role in the functional interaction of these cells during liver fibrosis induced by carbon tetrachloride. While hepatocyte-specific c-jun deletion led to increased fibrosis, the opposite outcome was observed when c-jun was deleted in both hepatocytes and KCs. Molecular analyses revealed compromised cytokine gene expression as the apical event related to the phenotype. Yet, purified hepatocytes from both mouse cohorts showed similar defects in cytokine gene expression. However, we noted increased macrophage infiltration in the absence of c-Jun in hepatocytes, which when chemically depleted, reversed the phenotype. Consistently, c-jun deletion in KCs alone also led to reduced fibrosis and cytokine gene expression. By contrast, c-jun deletion in hepatocytes and KCs did not affect the resolution phase after fibrotic injury. These data together demonstrate a pro-fibrogenic role for c-Jun in hepatocytes and KCs that functionally interact to regulate liver fibrosis. © 2021 Rockefeller University Press. All rights reserved.
dc.publisherRockefeller University Press
dc.rightsAttribution 4.0 International
dc.sourceScopus OA2021
dc.contributor.departmentINSTITUTE OF MOLECULAR & CELL BIOLOGY
dc.description.sourcetitleLife Science Alliance
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