Deletion of Wntless in myeloid cells exacerbates liver fibrosis and the ductular reaction in chronic liver injury
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- 作者：Katharine M. Irvine ; Andrew D. Clouston ; Victoria L. Gadd…
- 关键词：Liver fibrosis ; Ductular reaction ; Macrophages ; Matrix remodelling ; TAA ; CDE
- 刊名：Fibrogenesis & Tissue Repair
- 出版年：2015
- 出版时间：December 2015
- 年：2015
- 卷：8
- 期：1
- 全文大小：2,760 KB
- 刊物主题：Internal Medicine; Cell Biology;
- 出版者：BioMed Central
- ISSN：1755-1536
文摘
Background Macrophages play critical roles in liver regeneration, fibrosis development and resolution. They are among the first responders to liver injury and are implicated in orchestrating the fibrogenic response via multiple mechanisms. Macrophages are also intimately associated with the activated hepatic progenitor cell (HPC) niche or ductular reaction that develops in parallel with fibrosis. Among the many macrophage-derived mediators implicated in liver disease progression, a key role for macrophage-derived Wnt proteins in driving pro-regenerative HPC activation towards a hepatocellular fate has been suggested. Wnt proteins, in general, however, have been associated with both pro- and anti-fibrogenic activities in the liver and other organs. We investigated the role of macrophage-derived Wnt proteins in fibrogenesis and HPC activation in murine models of chronic liver disease by conditionally deleting Wntless expression, which encodes a chaperone essential for Wnt protein secretion, in LysM-Cre-expressing myeloid cells (LysM-Wls mice).