Expression of the ECM proteins fibulin-1 and -2 in acute and chronic liver disease and in cultured rat liver cells

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.

The fibulin-1 and fibulin-2 gene expression was analysed by immunohistochemistry, northern blot and real-time RT-PCR.

In normal rat livers, fibulin-1 and -2 were both located in the portal field and the walls of central vein. Fibulin-1 coding transcripts were detectable in the total RNA of normal rat liver, and fibulin-2 mRNA was only detected by sensitive real-time RT-PCR technique. Acute liver injury was characterized almost exclusively by an increased expression of fibulin-1, while that of fibulin-2 was not significantly modified. Both fibulin-1 and -2 expressions increased in cirrhosis. Fibulin-1 was extensively present in scars, whereas fibulin-2 localization was stronger along portal vessels. At a cellular level fibulin-1 was detectable in hepatocytes, hepatic stellate cells and liver myofibroblasts, whereas fibulin-2 was restricted to liver myofibroblasts.

In conclusion, fibulin-1 and -2 respond differentially to tissue injury. In chronically injured livers both molecules contribute to the hepatic tissue repair and extracellular matrix production.

Extracellular Matrix - Fibulin-1 - Fibulin-2 - Myofibroblast