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Cell‐specific Wnts Regulate Liver Zonation And Regeneration After Partial Hepatectomy
Author(s) -
Preziosi Morgan,
Yang Jing,
Okabe Hirohisa,
Diegel Cassandra,
Williams Bart,
Monga Satdarshan
Publication year - 2015
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.29.1_supplement.416.1
Subject(s) - wnt signaling pathway , liver regeneration , regeneration (biology) , knockout mouse , microbiology and biotechnology , biology , secretion , cell , chemistry , signal transduction , endocrinology , receptor , biochemistry
Our lab has previously shown that β‐catenin regulates liver zonation basally, and regeneration in a partial hepatectomy (Phx) model, under the control of Wnt and the canonical signaling pathway. Using cell‐specific Wntless (Wls) knockout mouse models, we determined epithelial cells are not the source of these Wnts. However, macrophage‐specific Wls knockouts demonstrated normal zonation but delayed regeneration, suggesting they are a contributing source of Wnts. We sought to further identify the source and identity of Wnts using stellate cell‐specific and endothelial cell‐specific Wls knockout models (HSC‐KO and EC‐KO, respectively). The HSC‐KO showed no deficit in regeneration or zonation, suggesting HSC are not the source of these Wnts. Interestingly, EC‐KO showed decreased zonation markers GS and Cyp2e1 at baseline, suggesting a contribution to zonation. Notably, macrophages and EC demonstrate high levels of Wnt2 and 9b at baseline, which significantly increase after Phx. Immunohistochemistry reveals Wnt2 and Wnt9b to be pericentrally localized to hepatocytes and EC, and diffuse throughout the liver one‐to‐three hour after Phx. Taken together, these results suggest that EC secretion of Wnt2 and Wnt9b is required for zonation and regeneration after Phx.