engleski

Immunohistochemistry of bone morphogenetic protein-9 in human liver

Background data. BMP-9, also referred to as growth/differentiation factor-2 (GDF-2) is a member of the transforming growth factor-beta superfamily of cytokines that regulate cell growth and differentiation in both embryonic and adult tissues. It is demonstrated that rhBMP-9, like some other members of the TGF-beta superfamily has the potential to initiate the osteoinductive cascade, but ability to induce osteogenesis is not developed like in some pther heterodimers such are BMP-4/7 and BMP-2/7. BMP-9 is predominantly expressed in liver and in cholinergic neurons. RhBMP-9 binds to receptors expressed on tumor liver cell line and stimulates their proliferation. Liver non-parenchimal cells contain an abundance of immunoreactive BMP-9 and those cells change phenotype in liver cirrhosis. Even BMP-9 receptor has not been identified yet, BMP-9-proregion complex binds to BMPRII in significant extent. BMP-9 is also involved in regulating glucose metabolism by lowering plasma glucose concentrations in normal and diabetic mice. Aims. To explore BMP-9 and BMP’ s receptors expression in human liver tissue and to analyze the pattern of this morphogenetic protein activity in healthy and disease organ. Methods. Immunolocalisation was performed using BMP-9 goat polyclonal antibody (Santa Cruzm CA, USA). Results. Positive activity of BMP-9 was found in: Infant’ s liver, fatty liver and cirrhotic liver. Except for positive hepatocytes, infant’ s liver is mostly positive in bile duct epithelial tissue cells located in fibrous tissue between lobes. Infant’ s hepatocytes as well as bile duct epithelial cells are positive to both BMPRI and BMPRII. Fatty liver is characterized with multiplying fibrous tissue in spaces between lobules and initial destruction of the bile duct epithelium. Intense positive intracellular cytoplasmatic staining is observed only in hepatocytes. Hepatocytes are positive for BMPRII and BMPRI, while bile duct epithelium expresses BMPRI. Hepatocytes in chronic liver are positive to BMP-9 antibody with less activity than fatty liver, but with more activity than in infant’ s liver. In liver cirrhosis hepatocytes as well as bile duct epithelium express BMPRI. Conclusion. BMP-9 and BMPs receptors are expressed in human liver. Activity of the BMP-9 antibody is more intense in fatty liver and cirrhotic liver than in healthy infant’ s liver. Therefore we presume that BMP-9 activity in human liver could be protective.

bone morphogenetic protein-9; immunohistochemistry; liver; BMP-receptors

DOI: 10.1007/s00223-007-9018-0