We have demonstrated anti-inflammatory, growth factor and anti-fibrotic activities of SCGB3A2 using mouse models with recombinant mouse SCGB3A2 protein. In order to provide evidence and warrant further development of recombinant SCGB3A2 as a therapeutic agent in treating patients suffering from various lung diseases, or pregnant mother facing premature birth, and/or preterm infants with respiratory distress, recombinant human SCGB3A2 was expressed, purified, and biochemically characterized in comparison to recombinant mouse SCGB3A2. Human SCGB3A2, as well as mouse SCGB3A2, readily formed a dimer in solution, and exhibited novel phospholipase A2 inhibitory activity. This was the first demonstration of any quantitative biochemical measurement for the evaluation of SCGB3A2 protein. Recombinant human SCGB3A2 was further evaluated for its development as a therapeutic agent in clinical settings using mouse models of lung development and fibrosis. Using the mouse as an experimental animal, recombinant human SCGB3A2 exhibited growth factor activity by promoting embryonic lung development in both ex vivo and in vivo systems. Anti-fibrotic activity was also evaluated using the bleomycin-induced lung fibrosis model, in which bleomycin-administered mice were intravenously given various doses of recombinant SCGB3A2 daily for 5 days starting 7 days after administration of bleomycin. All mice were subjected to necropsy on day 21. The best dose obtained for preventing fibrosis was 0.25 mg/kg/day. When SCGB3A2 was administered to pregnant female mice through the tail vein, the protein was detected in the dam's serum and lung, as well as the placenta, amniotic fluids and embryonic lungs at 10 min post-administration. The detection of recombinant human SCGB3A2 was carried out by a newly developed competitive ELISA system. These results suggested that SCGB3A2 readily crosses the placenta. Altogether, the studies using recombinant human SCGB3A2 in mouse models suggested that human SCGB3A2 can function as a growth factor and an anti-fibrotic agent in humans.
Showing the most recent 10 out of 30 publications
