19
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

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

      American Journal of Physiology - Cell Physiology
      Animals, Antigens, Human Platelet, metabolism, Arachidonic Acid, secretion, Autocrine Communication, drug effects, physiology, Cell Line, Transformed, Cyclic AMP, Cyclic AMP-Dependent Protein Kinases, antagonists & inhibitors, Cyclooxygenase 1, Cyclooxygenase 2, Cyclooxygenase 2 Inhibitors, Cyclooxygenase Inhibitors, pharmacology, Dinoprostone, Dose-Response Relationship, Drug, Epithelial Cells, Feedback, Isoenzymes, genetics, Kidney Diseases, physiopathology, Kidney Glomerulus, Kidney Tubules, Membrane Proteins, Mice, Prostaglandin-Endoperoxide Synthases, RNA, Messenger, Tetradecanoylphorbol Acetate

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          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.

          Related collections

          Author and article information

          Comments

          Comment on this article