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Congenital hepatic fibrosis is a rare disease characterized by portal tract fibrosis and biliary duct ectasia. It is associated with autosomal recessive polycystic kidney disease and rarely progresses to cirrhosis. The activated stellate cell has been implicated in the pathogenesis of alcohol- or inflammation-mediated cirrhosis through fibrogenic proteins such as transforming growth factor-β1; however, the role of the stellate cell in pure, noninflammatory fibrosis is unknown. It has been hypothesized that fibrosis in congenital hepatic fibrosis may be caused by upregulation of transforming growth factor-β1 and thrombospondin-1, and that the hepatic stellate cell may be the mediator of these proteins.Human liver tissue samples from patients with congenital hepatic fibrosis (n = 9) and from normal patients (n = 3) were analyzed. Tissue homogenates from both groups were analyzed for transforming growth factor-β1 protein and mRNA by Western blot analysis and in situ hybridization, respectively. Immunolocalization studies were performed in fixed tissue sections from both groups. Stellate cells were cultured from livers exhibiting congenital hepatic fibrosis and confirmed by desmin staining. The cells were cultured in serum-free medium for 48 hours, and media were collected and analyzed by Western blot analysis for thrombospondin-1 and transforming growth factor-β1.Congenital hepatic fibrosis liver tissue homogenates had higher levels of thrombospondin-1 and transforming growth factor-β1 protein than in normal livers. In congenital hepatic fibrosis tissue, transforming growth factor-β1 was more highly expressed in the ectatic biliary epithelium and the perisinusoidal space, whereas thrombospondin-1 localized most intensely to the hepatocytes and spared the bile ducts. Congenital hepatic fibrosis-derived stellate cells secreted both thrombospondin-1 and transforming growth factor-β1 in vitro.Transforming growth factor-β1 and thrombospondin-1 may play a role in the pathogenesis of liver fibrosis in patients with congenital hepatic fibrosis. One potential source of these fibrogenic proteins is the hepatic stellate cell.