Fibrogenesis in pediatric cholestatic liver disease: Role of taurocholate and hepatocyte-derived monocyte chemotaxis protein-1 in hepatic stellate cell recruitment #

• DOI: 10.1002/hep.22637
• Publication Date: 2008-09-19T16:52:36Z
• Authors: Grant A. Ramm; Ross W. Shepherd; Anita C. Hoskins; Sonia A. Greco; Agnieszka D. Ney; Tamara N. Pereira; Kim R. Bridle; James D. Doecke; Peter J. Meikle; Bruno Turlin; Peter J. Lewindon
• Keywords: Hepatic stellate cell; Monocyte; Liver disease

Abstract Cholestatic liver diseases, such as cystic fibrosis (CF) disease and biliary atresia, predominate causes of childhood cirrhosis. Despite diverse etiologies, the stereotypic final pathway involves fibrogenesis where hepatic stellate cells (HSCs) are recruited, producing excess collagen which initiates fibrosis. A possible molecular determinant this recruitment, monocyte chemotaxis protein-1 (MCP-1), an HSC-responsive chemokine, was investigated in CF atresia. The bile-duct-ligated rat vitro coculture models cholestatic injury were used to further explore role MCP-1 HSC recruitment proposed mechanism induction via bile acids. In both elevated expression predominated scar margin hepatocytes, closely associated with activated HSCs, also expressed cholangiocytes. Serum during early fibrogenesis. Similar observations made serum. Hepatocytes isolated from rats secreted increased avidly recruited HSCs coculture. This markedly inhibited interventional studies using anti-MCP-1 neutralizing antibody. disease, increased, positively correlating levels hydrophobic acid, taurocholate. rats, correlated taurocholate serum liver, negatively bile. normal human induced expression. Conclusion: These support hypothesis that up-regulation hepatocyte-derived MCP-1, by acids, results injury, is a key event these conditions. Therapies aimed at or acids may help reduce fibro-obliterative diseases. (Hepatology 2008.)