Non-Canonical Wnt Predominates in Activated Rat Hepatic Stellate Cells, Influencing HSC Survival and Paracrine Stimulation of Kupffer Cells

被引：35
作者：
Corbett, Laura [1 ]
Mann, Jelena [1 ]
Mann, Derek A. [1 ]
机构：
[1] Newcastle Univ, Fac Med Sci, Inst Cellular Med, Fibrosis Res Grp, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England
来源：
PLOS ONE | 2015年 / 10卷 / 11期
基金：
英国惠康基金;
关键词：
BETA-CATENIN; SIGNALING PATHWAYS; LIVER; PHOSPHORYLATION; APOPTOSIS; ADIPOGENESIS; EXPRESSION; QUIESCENT; PROTEINS; BINDING;
D O I：
10.1371/journal.pone.0142794
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
The Wnt system is highly complex and is comprised of canonical and non-canonical pathways leading to the activation of gene expression. Our aim was to examine changes in the expression of Wnt ligands and regulators during hepatic stellate cell (HSC) transdifferentiation and assess the relative contributions of the canonical and non-canonical Wnt pathways in fibrogenic activated HSC. The expression profile of Wnt ligands and regulators in HSC was not supportive for a major role for beta-catenin-dependent canonical Wnt signalling, this verified by inability to induce Topflash reporter activity in HSC even when expressing a constitutive active beta-catenin. We detected expression of Wnt5a in activated HSC which can signal via non-canonical mechanisms and showed evidence for non-canonical signalling in these cells involving phosphorylation of Dvl2 and pJNK. Stimulation of HSC or Kupffer cells with Wnt5a regulated HSC apoptosis and expression of TGF-beta 1 and MCP1 respectively. We were unable to confirm a role for beta-catenin-dependent canonical Wnt in HSC and instead propose autocrine and paracrine functions for Wnts expressed by activated HSC via non-canonical pathways. The data warrant detailed investigation of Wnt5a in liver fibrosis.
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页数：18
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