Unraveling the complexities of fibrosis and ductular reaction in liver disease: pathogenesis, mechanisms, and therapeutic insights.

Ductular reaction and fibrosis are hallmarks of many liver diseases including primary sclerosing cholangitis, primary biliary cholangitis, biliary atresia, alcoholic liver disease, and metabolic dysfunction-associated steatotic liver disease/metabolic dysfunction-associated steatohepatitis. Liver fibrosis is the accumulation of extracellular matrix often caused by excess collagen deposition by myofibroblasts. Ductular reaction is the proliferation of bile ducts (which are composed of cholangiocytes) during liver injury.

Mast Cell and Innate Immune Cell Communication in Cholestatic Liver Disease.

Mast cells (MCs) contribute to the pathogenesis of cholestatic liver diseases (primary sclerosing cholangitis [PSC] and primary biliary cholangitis [PBC]). PSC and PBC are immune-mediated, chronic inflammatory diseases, characterized by bile duct inflammation and stricturing, advancing to hepatobiliary cirrhosis. MCs are tissue resident immune cells that may promote hepatic injury, inflammation, and fibrosis formation by either direct or indirect interactions with other innate immune cells (neutrophils, macrophages/Kupffer cells, dendritic cells, natural killer, and innate lymphoid cells).

Knockout of secretin ameliorates biliary and liver phenotypes during alcohol-induced hepatotoxicity.

Background: Alcohol-related liver disease (ALD) is characterized by ductular reaction (DR), liver inflammation, steatosis, fibrosis, and cirrhosis. The secretin (Sct)/secretin receptor (SR) axis (expressed only by cholangiocytes) regulates liver phenotypes in cholestasis. We evaluated the role of Sct signaling on ALD phenotypes.

Loss of apical sodium bile acid transporter alters bile acid circulation and reduces biliary damage in cholangitis.

Primary sclerosing cholangitis (PSC) is characterized by increased ductular reaction (DR), liver fibrosis, hepatic total bile acid (TBA) levels, and mast cell (MC) infiltration. Apical sodium BA transporter (ASBT) expression increases in cholestasis, and ileal inhibition reduces PSC phenotypes. FVB/NJ and multidrug-resistant 2 knockout () mice were treated with control or ASBT Vivo-Morpholino (VM).