TY - JOUR
T1 - Group V secretory phospholipase A2 is involved in tubular integrity and sodium handling in the kidney
AU - Silva-Filho, João Luiz
AU - Peruchetti, Diogo Barros
AU - Moraes-Santos, Felipe
AU - Landgraf, Sharon Schilling
AU - Silva, Leandro Souza
AU - Sirtoli, Gabriela Modenesi
AU - Zamith-Miranda, Daniel
AU - Takiya, Christina Maeda
AU - Pinheiro, Ana Acacia Sá
AU - Diaz, Bruno Lourenço
AU - Caruso-Neves, Celso
N1 - Publisher Copyright:
© 2016 Silva-Filho et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2016/1/1
Y1 - 2016/1/1
N2 - Group V (GV) phospholipase A2 (PLA2) is a member of the family of secreted PLA2 (sPLA2) enzymes. This enzyme has been identified in several organs, including the kidney. However, the physiologic role of GV sPLA2 in the maintenance of renal function remains unclear. We used mice lacking the gene encoding GV sPLA2 (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 (FENa +) were also increased in PlA2g5-/- mice. The increased FENa + 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 sPLA2 is involved in the maintenance of tubular cell function and integrity, promoting sodium retention through increased cortical (Na+ + K+)-ATPase expression and activity.
AB - Group V (GV) phospholipase A2 (PLA2) is a member of the family of secreted PLA2 (sPLA2) enzymes. This enzyme has been identified in several organs, including the kidney. However, the physiologic role of GV sPLA2 in the maintenance of renal function remains unclear. We used mice lacking the gene encoding GV sPLA2 (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 (FENa +) were also increased in PlA2g5-/- mice. The increased FENa + 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 sPLA2 is involved in the maintenance of tubular cell function and integrity, promoting sodium retention through increased cortical (Na+ + K+)-ATPase expression and activity.
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U2 - 10.1371/journal.pone.0147785
DO - 10.1371/journal.pone.0147785
M3 - Article
C2 - 26820468
AN - SCOPUS:84958213320
SN - 1932-6203
VL - 11
JO - PloS one
JF - PloS one
IS - 1
M1 - e0147785
ER -