HGFL protein is a newly described glycoprotein made primarily by hepatocytes and secreted into plasma. Although the biological role of HGFL protein is not known, two functions have been suggested. The first function is as a growth factor to hepatocytes, based on the striking structural homology HGFL protein shares with hepatocyte growth factor (HGF). HGF is the most potent known mitogen to hepatocytes and is an important modulator of liver regeneration. HGF also has other tissue- and cell-specific functions, such as stimulation of cell migration and modulation of inflammation. The second function is as an activator of macrophages, based on the 97% amino acid sequence identity to macrophage stimulating protein (MSP). MSP is a recently described protein that induces morphologic changes, chemotaxis, and phagocytosis in peritoneal macrophages. Based on these data, Dr. Bezerra proposes that HGFL protein is a member of the HGF family of proteins and plans to directly assess the role of HGFL protein in liver regeneration and in activation of tissue macrophages. Specifically, he aims to test the ability of the protein to induce hepatocyte proliferation and activation of macrophages, to use these bioassays and recombinant mutants to assess the biological importance of the activation of the protein, and to assess the biological consequences of the in vivo loss of functional HGFL protein in a transgenic mouse model.
| Bezerra, J A; Bugge, T H; Melin-Aldana, H et al. (1999) Plasminogen deficiency leads to impaired remodeling after a toxic injury to the liver. Proc Natl Acad Sci U S A 96:15143-8 |
| Locaputo, S; Carrick, T L; Bezerra, J A (1999) Zonal regulation of gene expression during liver regeneration of urokinase transgenic mice. Hepatology 29:1106-13 |
| Bezerra, J A; Carrick, T L; Degen, J L et al. (1998) Biological effects of targeted inactivation of hepatocyte growth factor-like protein in mice. J Clin Invest 101:1175-83 |
