De rol van amphireguline bij Ischemie/reperfusieschade in de nier

The ErbB receptor family and his ligands, are involved in a lot of important cellular processes like migration, proliferation, differentiation, survival and the cell metabolism. The receptors are also involved in a lot of diseases like hypertension, arteriosclerosis and malignancies. The ErbB receptors in het kidney play an important role in the nephrogenesis, the renal electrolyte homeostasis and are also involved in a lot of kidney diseases. It is known that HB-EGF (an ErbB receptor ligand) has an early expression in the kidney shortly after induction of ischemia/reperfusion (IR) injury. HB-EGF knock-out mice show reduced damage in the kidney after IR injury with respect to the wild-type mice. This study will focus on the role of amphireguline (a different ErbB receptor ligand) in IR injury in the kidney. In human proximal tubular cells, amphiregulin induces proliferation. After induction of renal IR injury in the rat, the amphiregulin mRNA expression is up regulated 30 and 90 minutes after reperfusion. After 6 hours, the amphireguline mRNA expression level is lower in the treated rats than expression in the sham operated group and stays lower for three weeks. In human renal transplant donor biopsies, the amphiregulin mRNA expression 45 minutes after reperfusion is much higher than during the transplantation. The urine of healthy people almost contains no amphiregulin. Urine taken from transplant patient’s two days after transplantation, show a significant increase in urinary amphireguline. Amphiregulin is involved in the early phase after IR injury in the kidney.