CREPE: A First Mathematical Model for Crosstalking of Endothelial Cells and Hepatocyte Metabolism

Giuseppe Valvano, Gianni Orsi, Maria A. Guzzardi, Federico Vozzi, and Giovanni Vozzi


Computational Systems Biology, Cell cross-talk, Mathematical modeling, Endothelin-1, hepatocyte, endothelial cell


In liver there is a close coexistence between endothelial cells and hepatocytes. Endothelial cells mainly protect hepatocytes from blood vessel shear stress, acting as a barrier, but the interactions from these two cell types are several. A particular effect in hepatocyte-endothelial cross-talk is the reduction of glucose consumption respect to hepatocytes alone. Maybe hepatocytes reduce their glucose consumption supporting energy needs of endothelial cells. Monti et al. have studied the effects of Endothelin-1 on Glucokinase activity in adult rat hepatocytes. They observed a reduction in Glucokinase catalytic rate dependent of Endothelin-1 concentration. We developed CREPE (CRosstalking of Endothelial cells and hePatocytE metabolism), that is mathematical model of the Endothelin-1 mediated crosstalk between hepatocytes (HepG2) and endothelial cells (Human Umbilical Vein Endothelial Cells) in a traditional static co-culture system. CREPE was validated against experimental data, showing good agreement with them. So CREPE can be a starting point to develop predictive tools on complex and highly interconnected environment.

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