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Title: Functional interaction between macrophages and hepatocytes dictate the outcome of liver fibrosis
Authors: Xie, Min
Chia, Ren Hui
Li, Dan
Teo, Fanny Xueting
Krueger, Christian
Sabapathy, Kanaga 
Issue Date: 29-Jan-2021
Publisher: Rockefeller University Press
Citation: Xie, 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.
Rights: Attribution 4.0 International
Abstract: Hepatocytes 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.
Source Title: Life Science Alliance
ISSN: 2575-1077
DOI: 10.26508/lsa.202000803
Rights: Attribution 4.0 International
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