Abstract
Fibulin-2 was considered previously as a marker of rat liver myofibroblasts (rMF), but the role of fibulin-1 in acute or chronic liver damage is not investigated yet. Aim of this study was to evaluate the expression of fibulin-1 and -2 in rat models of liver damage and in human liver cirrhosis. Furthermore, the cellular sources of these proteins were also investigated.
Highlights
Liver fibrogenesis represents the uniform response of the liver to toxic, infectious, or metabolic agents and is characterized by an increased synthesis and altered depo-Cell Tissue Res (2009) 337:449–462 sition of newly formed extracellular matrix (ECM) components (Ramadori et al 1998)
Chemicals were obtained from the following sources: Dulbecco’s modification of Eagle’s medium (DMEM), M199 medium, and fetal calf serum (FCS) from Flow Laboratories (Bonn, Germany); endothelial cell basal medium (ECBM), human basic fibroblast growth factor, and human EFG from PromoCell (Heidelberg, Germany); pronase E from Merck (Darmstadt, Germany); collagenase from Clostridium histolyticum, random prime labeling kit, and dNTPs from Boehringer (Mannheim, Germany); insulin S from Hoechst (Frankfurt, Germany)
Fibulin-1 in normal rat livers was localized in the vessels of portal spaces (Fig. 1) and central veins
Summary
Liver fibrogenesis represents the uniform response of the liver to toxic, infectious, or metabolic agents and is characterized by an increased synthesis and altered depo-Cell Tissue Res (2009) 337:449–462 sition of newly formed extracellular matrix (ECM) components (Ramadori et al 1998). The composition in expanded portal areas, septa, and cirrhotic nodules is similar to that of the normal portal tracts and consists of collagens, various members of the structural glycoprotein family, the major subclasses of glycosaminoglycans, and elastin In addition to these classical matrix components, members of the coagulation system, such as fibrinogen/fibrin, plasmin, and von Willebrand factor (vWF; Knittel et al 1995; Neubauer et al 1995), participate in hepatic tissue repair. The fibulins are an emerging family of ECM proteins characterized by tandem arrays of calcium-binding epidermal growth factor (EGF)-like domains and a unique C-terminal structure (Timpl et al 2003) and are a broadly conserved component of the ECM (Hesselson and Kimble 2006) They were first discovered in 1989 (see Argraves et al 2003). Expression of the fibulin-2 gene is initiated later during embryonic development and is distributed in a more restricted manner than that of fibulin-1 (Zhang et al 1996)
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