Evolving concepts of liver fibrogenesis provide new diagnostic and therapeutic options.docVIP

Comparative Hepatology BioMedCentral Review Open Access Evolving concepts of liver fibrogenesis provide new diagnostic and therapeutic options Olav A Gressner, Ralf Weiskirchen and Axel M Gressner* Address: Institute of Clinical Chemistry and Pathobiochemistry, RWTH-University Hospital, Aachen, Germany Email: Olav A Gressner - ogressner@ukaachen.de; Ralf Weiskirchen - rweiskirchen@ukaachen.de; Axel M Gressner* - gressner@rwth-aachen.de * Corresponding author Published: 30 July 2007 Received: 30 May 2007 Accepted: 30 July 2007 Comparative Hepatology 2007, 6:7 doi:10.1186/1476-5926-6-7 This article is available from: /content/6/1/7 ? 2007 Gressner et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Despite intensive studies, the clinical opportunities for patients with fibrosing liver diseases have not improved. This will be changed by increasing knowledge of new pathogenetic mechanisms, which complement the canonical principle of fibrogenesis. The latter is based on the activation of hepatic stellate cells and their transdifferentiation to myofibroblasts induced by hepatocellular injury and consecutive inflammatory mediators such as TGF-β. Stellate cells express a broad spectrum of matrix components. New mechanisms indicate that the heterogeneous pool of (myo- )fibroblasts can be supplemented by epithelial-mesenchymal transition (EMT) from cholangiocytes and potentially also from hepatocytes to fibroblasts, by influx of bone marrow-derived fibrocytes in the damaged liver tissue and by differentiation of a subgroup of monocytes to fibroblasts after homing in the damaged tissue. These processes are regulated by the cytokines TGF-β and BMP-7, chemokines, colony-stimulating