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Figure 2 | Lipids in Health and Disease

Figure 2

From: Primary sclerosing cholangitis – The arteriosclerosis of the bile duct?

Figure 2

Model of the Development of Primary Sclerosing Cholangitis. (1) Toxic bile (e.g. toxic bile acids, oxidized/modified cholesterol and phospholipids) causes (2) the induction of a reactive phenotype of cholangiocytes characterized by de novo expression or overexpression of adhesion molecules, inflammatory and profibrogenetic cytokines, and receptors (e.g. TNF-α, TGF-β, toll-like receptors, VCAM, CD44). (3) Proinflammatory cytokines induce leakiness of the bile duct epithelium leading to regurgitation of bile into the portal space, leading to (4) transmigration of (5) neutrophils and (6) lymphocytes and their activation. Bile duct epithelial cell-derived growth factors and cytokines (e.g. TGF-β, PDGF) and reactive molecules released from neutrophils (7) (e.g. ROS, 4-HNE) stimulate extracellular matrix production, accumulation, and proliferation of (8) periductal myofibroblasts, leading to periductal fibrosis and in consequence to vascular deprivation of the bile duct system itself, causing (9) death of bile duct epithelial cells. Bile duct epithelial cell-derived growth factors (e.g. EGF, HGF, PDGF, BDNF) may also activate and recruit bone marrow derived progenitor cells into the portal field probably engaged in ductal reaction and proliferation of periductal MFBs.

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