Introduction and Aims: High levels of soluble urokinase-type Plasminogen Activator Receptor (suPAR) are associated with nephrotic syndrome and proteinuria in different nephropathies, including minimal change disease, focal segmental glomerulosclerosis and secondary glomerulonephritis.Osteopontin (OPN) is a pro-inflammatory cytokine which recently has been associated with kidney injury in lupus nephritis. However it is still uncertain if suPAR and OPN induce podocyte damage in vivo or if their increased levels are a consequence of kidney injury.
Methods: This study investigates the role of suPAR in inducing podocyte damage in animal models of lupus nephritis (MLR/lpr mice) and how suPAR is released from cultured monocytes. Moreover we will investigate the relationship between OPN and uPAR/suPAR expression on cultured monocytes.
Results: In the animal model, circulating suPAR level are increased during lupus nephritis and start to rise two weeks before the development of overt proteinuria (Fig. 1). On cultured monocytes, out of the tested drugs (furosemide, spironolactone, triamterene, valsartan, and unfractioned heparin), only captopril reduced the production of suPAR. This reduction is due to a lower cleavage from the cell’s plasma membrane, as membrane-uPAR expression slightly increases after captopril exposure (Fig. 2). On the other side, OPN increases suPAR release from cultured monocytes through the upregulation of uPAR mRNA, but does not increase the cleavage of membrane uPAR.
Conclusions: suPAR might be a mediator of podocyte damage in lupus nephritis because its levels rise before the development of proteinuria. Moreover circulating suPAR levels are influenced by both OPN levels and therapy with ACE-inhibitors, giving therefore a novel rationale for the use of ACE-inhibitors in lupus nephritis.
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