Journal Article

DKFZ-2025-00044

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png RAGE is a key regulator of ductular reaction-mediated fibrosis during cholestasis.

Lam, W. M. (First author)DKFZ* ; Gabernet, G. ; Poth, T. ; Sator-Schmitt, M.DKFZ* ; Oquendo, M. B. ; Walter, B.DKFZ* ; Lohr, S.DKFZ* ; De Ponti, A.DKFZ* ; Weiß, L.DKFZ* ; Schneider, M.DKFZ* ; Helm, D.DKFZ* ; Müller-Decker, K.DKFZ* ; Schirmacher, P. ; Heikenwälder, M.DKFZ* ; Klingmüller, U.DKFZ* ; Schneller, D.DKFZ* ; Geisler, F. ; Nahnsen, S. ; Angel, P. (Last author)DKFZ*

2025
Wiley Hoboken, NJ [u.a.]

This record in other databases:  

Please use a persistent id in citations: doi:10.1038/s44319-024-00356-7

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.

Keyword(s): Biliary Epithelial Cells ; Chronic Liver Injury ; Genetically Modified Mice ; Hepatic Stellate Cells ; Receptor for Advanced Glycation End Products

Note: DKFZ-ZMBH Alliance / 2025 Feb;26(3):880-907 / #EA:A100#LA:A100#

---

Contributing Institute(s):

1. Signaltransduktion/ Wachstumskontrolle (A100)
2. Proteomics (W120)
3. Gruppe Müller-Decker (W420)
4. Chronische Entzündung und Krebs (D440)
5. B200 Systembiologie der Signaltransduktion (B200)

Research Program(s):

1. 311 - Zellbiologie und Tumorbiologie (POF4-311) (POF4-311)

Appears in the scientific report 2025

---

Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Wiley ; Essential Science Indicators ; IF >= 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---