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| http://dx.doi.org/10.1016/j.jcmgh.2022.11.007 | DOI Listing |
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RAGE is a key regulator of ductular reaction-mediated fibrosis during cholestasis.
EMBO Rep
January 2025
Division of Signal Transduction and Growth Control, German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance, Heidelberg, Germany.
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.
View Article and Find Full Text PDFA heterogeneous subtype of biliary epithelial senescence may be involved in the pathogenesis of primary biliary cholangitis.
Clin Res Hepatol Gastroenterol
December 2024
Department of Pathology, Fukui Saiseikai Hospital, Fukui 918-8503, Japan.
Background & Aims: Biliary epithelial senescence is involved in the pathogenesis of primary biliary cholangitis (PBC). We hypothesized that a unique subtype of programmed death-ligand 1 (PD-L1)-positive senescent biliary epithelial cells (BECs) may be related to the pathogenesis of PBC in association with cyclic GMP-AMP synthase (cGAS)- stimulator of interferon genes (STING) pathway.
Approach & Results: The expression of PD-L1, STING and their association with senescent markers p16 and p21 were immunohistochemically determined in livers taken from the patients with PBC (n = 87) and 97 diseased and normal control livers.
[Study on the mechanism of Fuzheng Huayu formula against biliary fibrosis in mice].
Zhonghua Gan Zang Bing Za Zhi
November 2024
Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai201203, China Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shanghai Key Laboratory of Traditional Chinese Medicine, Shanghai201203, China.
Article Synopsis
- The study aimed to explore how the Fuzheng huayu formula (FZHY) affects biliary fibrosis in mice by comparing its effects with obeticholic acid (OCA) and a control group.
- Mice were treated with specific drugs over a 12-week period, and various liver health indicators, including serum enzyme levels and tissue markers, were analyzed using multiple biochemical techniques.
- Results demonstrated that both FZHY and OCA effectively reduced the harmful effects of fibrosis in the gene knockout mice by reversing elevated liver indicators, improving markers of liver function, and influencing specific molecular pathways related to inflammation and cellular response.
Extracellular matrix protein 1 binds to connective tissue growth factor against liver fibrosis and ductular reaction.
Hepatol Commun
November 2024
Department of Pathology, Tulane University, New Orleans, Louisiana, USA.
Background: Extracellular matrix protein 1 (ECM1) can inhibit TGFβ activation, but its antifibrotic action remains largely unknown. This study aims to investigate ECM1 function and its physical interaction with the profibrotic connective tissue growth factor (CTGF) in fibrosis and ductular reaction (DR).
Methods: Ecm1 knockouts or animals that ectopically expressed this gene were subjected to induction of liver fibrosis and DR by feeding 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) or α-naphthyl-isothiocyanate (ANIT).
Osteopontin Promotes Cholangiocyte Secretion of Chemokines to Support Macrophage Recruitment and Fibrosis in MASH.
Liver Int
October 2024
Regeneration and Repair, Institute of Hepatology, Foundation for Liver Research, London, UK.
Background And Aims: Osteopontin (OPN) promotes the ductular reaction and is a major driver of chronic liver disease (CLD) progression. Although CLD is characterised by the accumulation of inflammatory cells including macrophages around the peri-portal regions, the influence of OPN on recruitment is unclear. We investigated the role of OPN in cholangiocyte chemokine production and macrophage recruitment by combining in vivo, in vitro, and in silico approaches.
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