Open AccessHepatic stellate cell‐expressed endosialin balances fibrogenesis and hepatocyte proliferation during liver damage
Author(s) -
Mogler Carolin,
Wieland Matthias,
König Courtney,
Hu Junhao,
Runge Anja,
Korn Claudia,
Besemfelder Eva,
BreitkopfHeinlein Katja,
Komljenovic Dorde,
Dooley Steven,
Schirmacher Peter,
Longerich Thomas,
Augustin Hellmut G
Publication year - 2015
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201404246
Subject(s) - hepatic stellate cell , hepatocyte , microbiology and biotechnology , liver cytology , cell growth , cancer research , biology , chemistry , liver metabolism , endocrinology , biochemistry , in vitro
Liver fibrosis is a reversible wound‐healing response to injury reflecting the critical balance between liver repair and scar formation. Chronic damage leads to progressive substitution of liver parenchyma by scar tissue and ultimately results in liver cirrhosis. Stromal cells (hepatic stellate cells [ HSC ] and endothelial cells) have been proposed to control the balance between liver fibrosis and regeneration. Here, we show that endosialin, a C‐type lectin, expressed in the liver exclusively by HSC and portal fibroblasts, is upregulated in liver fibrosis in mouse and man. Chronic chemically induced liver damage resulted in reduced fibrosis and enhanced hepatocyte proliferation in endosialin‐deficient ( EN KO ) mice. Correspondingly, acute‐liver‐damage‐induced hepatocyte proliferation (partial hepatectomy) was increased in EN KO mice. A candidate‐based screen of known regulators of hepatocyte proliferation identified insulin‐like growth factor 2 ( IGF 2) as selectively endosialin‐dependent hepatocyte mitogen. Collectively, the study establishes a critical role of HSC in the reciprocal regulation of fibrogenesis vs. hepatocyte proliferation and identifies endosialin as a therapeutic target in non‐neoplastic settings.