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Wnt/β‐catenin signaling in liver regeneration (398.5)
Author(s) -
Yang Jing,
Okabe Hirohisa,
Williams Bart,
Monga Satdarshan
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.398.5
Subject(s) - wnt signaling pathway , microbiology and biotechnology , hepatocyte , lrp5 , lrp6 , liver regeneration , beta catenin , catenin , chemistry , secretion , population , signal transduction , biology , medicine , endocrinology , regeneration (biology) , biochemistry , in vitro , environmental health
β‐catenin plays a critical role in triggering liver regeneration (LR) after partial hepatectemy (PH). β‐catenin can be activated by numerous pathways, the primary one being Wnt signaling. Defect of β‐catenin leads to delay of LR in hepatocyte specific β‐catenin knockout mice (KO1). Ablation of Wnt‐dependent β‐catenin signaling in hepatocyte specific LRP5/6 double knockouts (KO2) also results in suboptimal LR after PH, which phenocopies KO1. Therefore, Wnt signaling is the major signaling pathway that activates β‐catenin during LR. To further elucidate the source of Wnts in the liver, we studied Wnts secretion from different hepatic cell population after PH. Wingless (Wls) is a critical regulator of Wnt secretion. We generated hepatocyte and macrophage specific Wls knockout mice (KO3&KO4, respectively), which lack the ability of hepatocytes and macrophages to secrete Wnts, respectively. KO3 had normal initiation of LR, while depletion of Wls from macrophages leads to suboptimal LR and impaired β‐catenin activation. Therefore, macrophages but not hepatocytes are responsible for Wnt secretion and β‐catenin activation during LR after PH.