Is the Pseudoxanthoma Elasticum (PXE) a purinergic disease?

Mutations in the human ABCC6 gene, a member of ABCs protein superfamily that encodes MRP6 protein which is involved in multi-drug resistance phenomena [1], cause Pseudoxanthoma Elasticum (PXE), a multisystemic disorder characterized by progressive ectopic calcification of the mineralized elastic fibers in dermal, ocular and vascular tissues [2]. MRP6 is mainly present in liver and in kidney, especially in the basolateral plasma membrane of hepatocytes, and it was found that MRP6 is involved in the release of ATP out of the cell. ATP is immediately hydrolyzated in adenosine and in PPi (a mineralization inhibitor) by ENPP1 and CD73 proteins [3]. In order to characterize the role of ABCC6 in hepatic cells and in the physiopathology of PXE, ABCC6 gene expression was silenced in HepG2 cells. In HepG2 cells with silenced ABCC6, a variation of expression in genes involved in mineralization processes and a downregulation of NT5E gene have been observed [2]. In this work the effects of an inhibitor of ABC proteins activity in HepG2 cells have been evaluated. The results obtained show that, in the presence of this inhibitor, both CD73 and MRP6 protein levels are downregulated, while TNAP protein level is unchanged. In order to characterize the effects of the inhibition of purinergic pathway due to MRP6 low activity, the HepG2 cells were treated with this inhibitor in the presence and in the absence of adenosine. The results obtained show that there is a variation of genes involved in mineralization processes regulated by the purinergic pathway, such as NT5E and TNAP.