Role of cyclic AMP in idiopathic nephrotic syndrome: A pathway involving adecrease in glomerular cell heparan sulfates?

The physiopathological mechanisms of idiopathic nephrotic syndrome involve a circulating plasma factor and a decrease in HS in the glomerular basement membrane. Previous studies have demonstrated that plasma from patients wit h INS decreases glomerular cell HS in vitro. We examined the involvement of cyclic adenosine monophosphate (cAMP) in this interaction. We studied the effect of plasma from patients with INS on mesangial cell cAMP. We also det ermined mesangial cell HS when cAMP levels were modified using a cationic m embrane after metabolic labeling. Cellular cAMP levels increased significan tly when mesangial cells were incubated with plasma from patients with INS in comparison with control plasma (+77%, P = 0.01). Forskolin and IBMX, whi ch increased cellular cAMP, decreased HS levels (-21 +/- 9% and -15 +/- 6% respectively, P < 0.05 for both), whereas dideoxyadenosine, which decreased cellular cAMP, increased HS levels (+24 +/- 7%, P < 0.05). Plasma from pat ients with INS decreased glomerular cell HS in comparison with control plas ma (-34 +/- 8%, P < 0,05). This effect was abolished when cells were preinc ubated with ddAdo to prevent an increase in cAMP levels. We conclude that i n mesangial cells, plasma from patients with INS increases cAMP levels, and that cAMP mediates a decrease in HS levels. Moreover, the action of plasma from patients on HS was inhibited when an increase in cAMP was prevented. cAMP may therefore be instrumental in the negative effect of the plasma fac tor on mesangial cell HS. (C) 2000 Wiley-Liss, Inc.