방사무늬 김 (Pyropia Yezoensis)에서 얻은 Cyclophilin의 소장상피세포 증식 효과

Abstract

Pyropia yezoensis (P. yezoensis) is a marine algae that has antioxidant, anti-inflammatory, antitumor and anti-aging activities. Cyclophilin (Cyp), known as Peptidyl-prolyl isomerase (PPIase), has many function that include immune response regulation, antioxidants, cell proliferation regulation etc. Recombinant Cyp from red algae, is known to effect on development and growth of organism and it has effect of antioxidants and antifungal activity. But, other biological effect of recombinant Cyp is unclear. Intestinal epithelial cells have a life span of 3 to 5 days and maintain their population by periodic proliferation. When they are damaged, they recover the injured area through proliferation. So, intestinal epithelial cell proliferation is essential. In this study, we examined effect of recombinant Cyp from Pyropia yezoensis (pyCyp) on IEC-6 cells. First, the MTS assay showed that pyCyp increased cell proliferation in a dose-dependent manner. We focused on two cell proliferation mechanism. One is IGF-IR signaling pathway, the other is EGFR signaling pathway. Both of the signaling pathway are essential in regulation of cell growth, proliferation and survival. pyCyp stimulate IGF-IR that induce intracellular signal transduction cascades, including the phosphatidylinositol 3-kinase (PI3K)/Akt pathway and mTOR pathway. EGFR stimulated by pyCyp induce intracellular signaling pathway including Ras signaling pathway. Also, we observed cell cycle related protein. pyCyp increased expression of Cyclin A, Cyclin E, Cdk2 and decreased in protein levels of p27 and p21. It means pyCyp promote Cell cycle progression by increasing S phase percent. These results indicate that pyCyp stimulate cell proliferation via IGF-IR and EGFR signaling pathway that induce downstream signaling pathway and promote cell cycle progression in intestinal epithelial cell and have important implication for understanding the function of pyCyp purified from Pyropia yezoensis.