PGE2 reduces arachidonic acid release in murine podocytes: evidence for an autocrine feedback loop.

Abstract

Increased glomerular prostaglandin E(2) (PGE(2)) production is associated with the progression of diseases such as membranous nephropathy, nephrotic syndrome, and anti-Thy1 nephritis. We investigated the signaling pathways that regulate the synthesis and actions of PGE(2) in glomerular podocytes. To study its actions, we assessed the ability of PGE(2) to regulate the production of its own precursor, arachidonic acid (AA), in a mouse podocyte cell line. PGE(2) dose-dependently reduced phorbol ester (PMA)-mediated AA release. Inhibition of PMA-stimulated AA release by PGE(2) was found to be cAMP/PKA-dependent, because PGE(2) significantly increased levels of this second messenger, whereas the inhibitory actions of PGE(2) were reversed by PKA inhibition and reproduced by the cAMP-elevating agents forskolin and IBMX. PGE(2) synthesis in this podocyte cell line increased fourfold at 60 min in response to PMA, coinciding with upregulation of cyclooxygenase (COX)-2 but not COX-1 levels. However, PGE(2) synthesis was significantly reduced by COX-1-selective inhibition, yet to a lesser extent by COX-2-selective inhibition. Our findings suggest that PMA-stimulated PGE(2) synthesis in mouse podocytes requires both basal COX-1 activity and induced COX-2 expression, and that PGE(2) reduces PMA-stimulated AA release in a cAMP/PKA-dependent manner. Such an autocrine regulatory loop might have important consequences for podocyte and glomerular function in the context of renal diseases involving PGE(2) synthesis.

050100150'04'05'06'07'08'09'10'11'12'13'14'15'16'17
Citations per Year

321 Citations

Semantic Scholar estimates that this publication has 321 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Lemieux2003PGE2RA, title={PGE2 reduces arachidonic acid release in murine podocytes: evidence for an autocrine feedback loop.}, author={Lyne I Lemieux and Sherine S Rahal and Christopher R. J. Kennedy}, journal={American journal of physiology. Cell physiology}, year={2003}, volume={284 2}, pages={C302-9} }