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000296114 1001_ $$0P:(DE-HGF)0$$aLam, Wai-Ling Macrina$$b0$$eFirst author
000296114 245__ $$aRAGE is a key regulator of ductular reaction-mediated fibrosis during cholestasis.
000296114 260__ $$aHoboken, NJ [u.a.]$$bWiley$$c2025
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000296114 520__ $$aDuctular reaction (DR) is the hallmark of cholestatic diseases manifested in the proliferation of bile ductules lined by biliary epithelial cells (BECs). It is commonly associated with an increased risk of fibrosis and liver failure. The receptor for advanced glycation end products (RAGE) was identified as a critical mediator of DR during chronic injury. Yet, the direct link between RAGE-mediated DR and fibrosis as well as the mode of interaction between BECs and hepatic stellate cells (HSCs) to drive fibrosis remain elusive. Here, we delineate the specific function of RAGE on BECs during DR and its potential association with fibrosis in the context of cholestasis. Employing a biliary lineage tracing cholestatic liver injury mouse model, combined with whole transcriptome sequencing and in vitro analyses, we reveal a role for BEC-specific Rage activity in fostering a pro-fibrotic milieu. RAGE is predominantly expressed in BECs and contributes to DR. Notch ligand Jagged1 is secreted from activated BECs in a Rage-dependent manner and signals HSCs in trans, eventually enhancing fibrosis during cholestasis.
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000296114 650_7 $$2Other$$aBiliary Epithelial Cells
000296114 650_7 $$2Other$$aChronic Liver Injury
000296114 650_7 $$2Other$$aGenetically Modified Mice
000296114 650_7 $$2Other$$aHepatic Stellate Cells
000296114 650_7 $$2Other$$aReceptor for Advanced Glycation End Products
000296114 7001_ $$aGabernet, Gisela$$b1
000296114 7001_ $$aPoth, Tanja$$b2
000296114 7001_ $$0P:(DE-He78)2119821cf3458781f06157c7aeecba8b$$aSator-Schmitt, Melanie$$b3$$udkfz
000296114 7001_ $$00000-0003-4221-5723$$aOquendo, Morgana Barroso$$b4
000296114 7001_ $$0P:(DE-He78)417337e7f94f6e1325a168191cbdc4f1$$aWalter, Bettina$$b5$$udkfz
000296114 7001_ $$0P:(DE-He78)d7efff917864e0e86459893cf0e83a99$$aLohr, Sabrina$$b6$$udkfz
000296114 7001_ $$0P:(DE-He78)8f8d4ec0bcab2ba838bc964b2e684808$$aDe Ponti, Aurora$$b7
000296114 7001_ $$0P:(DE-He78)59998caf619d8669efab21372b1a2787$$aWeiß, Lena$$b8
000296114 7001_ $$0P:(DE-He78)0d37cc734b95fed555f2244d6fee6320$$aSchneider, Martin$$b9$$udkfz
000296114 7001_ $$0P:(DE-He78)daaed5a5b968028e6e95d273150d5ab1$$aHelm, Dominic$$b10$$udkfz
000296114 7001_ $$0P:(DE-He78)799d978330dff449f8244947929a4518$$aMüller-Decker, Karin$$b11
000296114 7001_ $$aSchirmacher, Peter$$b12
000296114 7001_ $$0P:(DE-He78)66ed2d4ec9bc11d29b87ac006adf85e5$$aHeikenwälder, Mathias$$b13$$udkfz
000296114 7001_ $$0P:(DE-He78)860df4ab16c373fb28a815dcd81107a6$$aKlingmüller, Ursula$$b14$$udkfz
000296114 7001_ $$0P:(DE-He78)172f117444a06f0aaba2d86c322f7eb2$$aSchneller, Doris$$b15$$udkfz
000296114 7001_ $$aGeisler, Fabian$$b16
000296114 7001_ $$aNahnsen, Sven$$b17
000296114 7001_ $$0P:(DE-He78)f4f068e71e0d87bf0ad51e6214ab84e9$$aAngel, Peter$$b18$$eLast author$$udkfz
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