Selectins are cell membrane glycoproteins that recognize specific glycoconjugates expressed on the surface of cells. Then, selectins adjust cell-cell interactions that are important in inflammation, hemostasis and cancer metastasis. Selectins mediate leukocyte calls to move into the site of inflammation through interactions with activated endothelial cells or endogenous selectin ligands expressed in high endothelial venules. Types of selectins are divided into L-selectin, E-selectin and P-selectin, which are called to CD62L, CD62E, and CD62P, respectively. Each selectin is composed of four regions; the C-type lectin region of N-terminal, the epidermal growth factor (EGF) region, the intracellular C-terminal region, and the hydrophobic transmembrane region. They have similar structures but differ in their binding specificities and tissue distributions. The selectin family commonly recognizes the sialyl Lewis X (sLeX) on carbohydrate structures. Although biological ligands bound to each selectin are different from each other, they commonly bind to P-selectin glycoprotein ligand-1 (PSGL-1) ligand. The PSGL-1 ligand is a glycoprotein promoting cell adhesion in inflammatory responses. If the absence of selectins and their ligands in humans and animals are, should lead to persistent infections and diseases. Selectin family must be considered as a key subject for drug discovery since they have various functions depending on the ligand which they bind to.

Expression of epithelial cell adhesion molecule (EpCAM) in the early phase of hepatocarcinogenesis induced by diethylnitrosamine (DEN) was investigated. At 14 days of age, 60 ICR mice were divided into two groups and treated with saline (group 1) or DEN (group 2, 10 mg/kg of body weight, i.p. injection), and were sacrificed at 6 h and 1, 2, 3, 7, and 28 days after treatment with saline or DEN. During necropsy, half of the liver from saline- or DEN-treated mice was processed for histopathological examination and immunohistochemical staining of EpCAM and apoptosis. The remaining liver tissue was snap-frozen in liquid nitrogen for RNA extraction and analysis of EpCAM mRNA expression. Immunohistochemical examination showed that EpCAM expression was detected only in a small number of hepatocytes from saline-treated mice and its expression was detected in bile duct cells and round cells around portal areas, as well as hepatocytes in the livers of DEN-treated mice. In addition, multiple apoptotic cells were found in the livers of mice treated with DEN. EpCAM mRNA expression was significantly higher in DEN-treated mice at 1, 7, and 28 days compared to saline-treated mice at 6 h (P<0.01). Taken together, EpCAM expression and apoptosis were increased in liver by DEN treatment.

The shortage of human organs for transplantation has induced the research on the possibility of using animal as porcine. However, pig to human transplantation as known as xeno-transplantation has major problem as immunorejection. Recently, the solutions of pig to human xenotransplantation are commonly mentioned as having a genetically modification which include alpha 1, 3 galatosyl transferase knockout (GTKO) and immune-suppressing gene transgenic model. Unfortunately, the expression level of transgenic gene is very low activity. Therefore, development of gene overexpression system is the most urgent issue. Also, the tissue specific overexpression system is very important. Because most blood vessels are endothelial cells, establishment of the endothelial-specific promoter is attractive candidates for the introduction of suppressing immunorejection. In this study, we focus the ICAM2 promoter which has endothelial-specific regulatory region. To detect the regulatory region of ICAM2 promoter, we cloned 3.7 kb size mini-pig ICAM2 promoter. We conduct serial deletion of 5' flanking region of mini-pig ICAM2 promoter then selected promoter size as 1 kb, 1.5 kb, 2 kb, 2.5 kb, and 3 kb. To analyze promoter activity, luciferase assay system was conducted among these vectors and compare endothelial activity with epithelial cells. The reporter gene assay revealed that ICAM2 promoter has critical activity in endothelial cells (CPAE) and 1 kb size of ICAM2 promoter activity was significantly increased. Taken together, our studies suggest that mini-pig ICMA2 promoter is endothelial cell specific overexpression promoter and among above all size of promoters, 1 kb size promoter is optimal candidate to overcome the vascular immunorejection in pig to human xenotransplantation.