Visceral glomerular epithelial cells (GEC) are crucial for glomerular permselectivity and structural integrity in the kidney. The current study addressed the role of
cyclooxygenase (COX)-2 and its product
prostaglandin (PG) E2 in GEC survival. We generated a subclone of cultured rat GEC, which overexpress COX-2 in an inducible manner. When COX-2 was induced, GEC survived better in serum-deprived conditions. Induction of COX-2 was correlated with increased
PGE2 generation, increased activation of
extracellular signal-regulated kinase, decreased apoptosis, and increased cell proliferation. Rat GEC abundantly expressed the EP4
isoform of
PGE2 receptor. Induction of COX-2 and addition of exogenous
PGE2 both lead to decreased serum deprivation-induced apoptosis, which was accompanied by activation of the survival
kinase Akt. Anti-apoptotic effect of COX-2 induction was reversed by the specific inhibitor of the EP4 receptor,
L-161982.
PGE2 also inhibited
puromycin aminonucleoside-induced GEC apoptosis in vitro. Acute
puromycin aminonucleoside nephrosis (PAN) is a rat model of GEC injury and
proteinuria. In rats with PAN, glomerular apoptosis, quantified as
caspase-3 activity, as well as urinary
protein excretion were significantly increased, compared with control rats. Administration of
L-161982 in rats with PAN further exacerbated
caspase-3 activation and
proteinuria. Thus COX-2 and its product
PGE2 may have anti-apoptotic/protective effect on GEC via the EP4 receptor of
PGE2.