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@ARTICLE{Lam:296114,
author = {W. M. Lam$^*$ and G. Gabernet and T. Poth and M.
Sator-Schmitt$^*$ and M. B. Oquendo and B. Walter$^*$ and S.
Lohr$^*$ and A. De Ponti$^*$ and L. Weiß$^*$ and M.
Schneider$^*$ and D. Helm$^*$ and K. Müller-Decker$^*$ and
P. Schirmacher and M. Heikenwälder$^*$ and U.
Klingmüller$^*$ and D. Schneller$^*$ and F. Geisler and S.
Nahnsen and P. Angel$^*$},
title = {{RAGE} is a key regulator of ductular reaction-mediated
fibrosis during cholestasis.},
journal = {EMBO reports},
volume = {26},
number = {3},
issn = {1469-221X},
address = {Hoboken, NJ [u.a.]},
publisher = {Wiley},
reportid = {DKFZ-2025-00044},
pages = {880-907},
year = {2025},
note = {DKFZ-ZMBH Alliance / 2025 Feb;26(3):880-907 /
#EA:A100#LA:A100#},
abstract = {Ductular reaction (DR) is the hallmark of cholestatic
diseases manifested in the proliferation of bile ductules
lined by biliary epithelial cells (BECs). It is commonly
associated with an increased risk of fibrosis and liver
failure. The receptor for advanced glycation end products
(RAGE) was identified as a critical mediator of DR during
chronic injury. Yet, the direct link between RAGE-mediated
DR and fibrosis as well as the mode of interaction between
BECs and hepatic stellate cells (HSCs) to drive fibrosis
remain elusive. Here, we delineate the specific function of
RAGE on BECs during DR and its potential association with
fibrosis in the context of cholestasis. Employing a biliary
lineage tracing cholestatic liver injury mouse model,
combined with whole transcriptome sequencing and in vitro
analyses, we reveal a role for BEC-specific Rage activity in
fostering a pro-fibrotic milieu. RAGE is predominantly
expressed in BECs and contributes to DR. Notch ligand
Jagged1 is secreted from activated BECs in a Rage-dependent
manner and signals HSCs in trans, eventually enhancing
fibrosis during cholestasis.},
keywords = {Biliary Epithelial Cells (Other) / Chronic Liver Injury
(Other) / Genetically Modified Mice (Other) / Hepatic
Stellate Cells (Other) / Receptor for Advanced Glycation End
Products (Other)},
cin = {A100 / W120 / W420 / D440 / B200},
ddc = {570},
cid = {I:(DE-He78)A100-20160331 / I:(DE-He78)W120-20160331 /
I:(DE-He78)W420-20160331 / I:(DE-He78)D440-20160331 /
I:(DE-He78)B200-20160331},
pnm = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
pid = {G:(DE-HGF)POF4-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39747668},
doi = {10.1038/s44319-024-00356-7},
url = {https://inrepo02.dkfz.de/record/296114},
}