Altered Expression of Renal AQP1, AQP2 and NHE3 in Puromycin Aminonucleoside Induced Nephrotic Syndrome: Intervention by Alpha-MSH Treatment / 대한신장학회잡지

ABSTRACT

BACKGROUND: We examined whether puromycin aminonucleoside (PAN)-induced nephrotic syndrome (NS) is associated with altered renal handling of water and sodium along with changes of renal abundance of aquaporins (AQP1 and AQP2) and NHE3. Next we tested the effects of alpha-melanocyte stimulating hormone (alpha- MSH), a potent anti-inflammatory drug, on the PAN-induced renal functional derangement and the changes of renal AQPs and NHE3 abundance. METHODS: PAN was administered to Sprague-Dawley rats using two protocols protocol 1 (180 mg/kg, single iv injection) and protocol 2 (100 mg/kg, single iv injection). RESULTS: In both protocols, PAN-induced NS was associated with decreased urine concentration, manifested by an increased urine output and decreased urine osmolality and TcH2O. Consistent with this, a marked downregulation of vasopressin-regulated collecting duct AQP2 expression was seen in PAN-induced NS. In protocol 2 where rats treated with moderate dose of PAN, alpha-MSH cotreatment prevented the reduction of urine osmolality and the increase of the FENa in the PAN-induced NS. This suggests that alpha-MSH may have protective effects against the renal functional deterioration induced by PAN. The renal abundance of the AQP1, AQP2 and NHE3 was reduced in PAN-induced NS in protocol 2, as seen in protocol 1. In contrast to the functional improvement, alpha-MSH cotreatment had marginal effects in the prevention of renal AQP1, AQP2 and NHE3 downregulation in PAN-induced NS. CONCLUSION: PAN-induced NS was associated with decreased urine concentration along with reduced renal AQP2, AQP1 and NHE3 abundance. Alpha-MSH may have protective effects against the renal functional deterioration (e.g., urine osmolality and FENa). However, alpha-MSH treatment alone is less likely to prevent the marked reduction of AQP2, AQP1 and NHE3 abundance in PAN-induced NS, in contrast to the previously known dramatic effects against the ischemia-reperfusion injury in kidney and small intestine.