Group V Secretory Phospholipase A(2) Is Involved in Tubular Integrity and Sodium Handling in the Kidney

Group V (GV) phospholipase A(2) (PLA(2)) is a member of the family of secreted PLA(2) (sPLA2) enzymes(.) This enzyme has been identified in several organs, including the kidney. However, the physiologic role of GV sPLA(2) in the maintenance of renal function remains unclear. We used mice lacking the gene encoding GV sPLA(2) (Pla2g5(−/−)) and wild-type breeding pairs in the experiments. Mice were individually housed in metabolic cages and 48-h urine was collected for biochemical assays. Kidney samples were evaluated for glomerular morphology, renal fibrosis, and expression/activity of the (Na(+) + K(+))-ATPase α1 subunit. We observed that plasma creatinine levels were increased in Pla2g5(−/−) mice following by a decrease in creatinine clearance. The levels of urinary protein were higher in Pla2g5(−/−) mice than in the control group. Markers of tubular integrity and function such as γ-glutamyl transpeptidase, lactate dehydrogenase, and sodium excretion fraction (FE(Na)(+)) were also increased in Pla2g5(−/−) mice. The increased FE(Na)(+) observed in Pla2g5(−/−) mice was correlated to alterations in cortical (Na(+) + K(+)) ATPase activity/ expression. In addition, the kidney from Pla2g5(−/−) mice showed accumulation of matrix in corticomedullary glomeruli and tubulointerstitial fibrosis. These data suggest GV sPLA(2) is involved in the maintenance of tubular cell function and integrity, promoting sodium retention through increased cortical (Na(+) + K(+))-ATPase expression and activity.