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@ARTICLE{Mogler:127165,
author = {C. Mogler$^*$ and M. Wieland$^*$ and C. König$^*$ and J.
Hu and A. Runge$^*$ and C. Korn$^*$ and E. Besemfelder$^*$
and K. Breitkopf-Heinlein and D. Komljenovic$^*$ and S.
Dooley and P. Schirmacher and T. Longerich and H.
Augustin$^*$},
title = {{H}epatic stellate cell-expressed endosialin balances
fibrogenesis and hepatocyte proliferation during liver
damage.},
journal = {EMBO molecular medicine},
volume = {7},
number = {3},
issn = {1757-4684},
address = {Weinheim},
publisher = {Wiley-VCH},
reportid = {DKFZ-2017-03191},
pages = {332 - 338},
year = {2015},
abstract = {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 (IGF2) 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.},
keywords = {Antigens, CD (NLM Chemicals) / Antigens, Neoplasm (NLM
Chemicals) / CD248 protein, human (NLM Chemicals) / Neoplasm
Proteins (NLM Chemicals) / tumor endothelial marker 1, mouse
(NLM Chemicals)},
cin = {A190 / L101 / E020},
ddc = {610},
cid = {I:(DE-He78)A190-20160331 / I:(DE-He78)L101-20160331 /
I:(DE-He78)E020-20160331},
pnm = {311 - Signalling pathways, cell and tumor biology
(POF3-311)},
pid = {G:(DE-HGF)POF3-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:25680861},
pmc = {pmc:PMC4364949},
doi = {10.15252/emmm.201404246},
url = {https://inrepo02.dkfz.de/record/127165},
}