Blog
About

0
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Concerted EP2 and EP4 Receptor Signaling Stimulates Autocrine Prostaglandin E 2 Activation in Human Podocytes

      Read this article at

      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

          Glomerular hyperfiltration is an important mechanism in the development of albuminuria. During hyperfiltration, podocytes are exposed to increased fluid flow shear stress (FFSS) in Bowman’s space. Elevated Prostaglandin E2 (PGE 2) synthesis and upregulated cyclooxygenase 2 (Cox2) are associated with podocyte injury by FFSS. We aimed to elucidate a PGE 2 autocrine/paracrine pathway in human podocytes (hPC). We developed a modified liquid chromatography tandem mass spectrometry (LC/ESI-MS/MS) protocol to quantify cellular PGE 2, 15-keto-PGE 2, and 13,14-dihydro-15-keto-PGE 2 levels. hPC were treated with PGE 2 with or without separate or combined blockade of prostaglandin E receptors (EP), EP2, and EP4. Furthermore, the effect of FFSS on COX2, PTGER2, and PTGER4 expression in hPC was quantified. In hPC, stimulation with PGE 2 led to an EP2- and EP4-dependent increase in cyclic adenosine monophosphate (cAMP) and COX2, and induced cellular PGE 2. PTGER4 was downregulated after PGE 2 stimulation in hPC. In the corresponding LC/ESI-MS/MS in vivo analysis at the tissue level, increased PGE 2 and 15-keto-PGE 2 levels were observed in isolated glomeruli obtained from a well-established rat model with glomerular hyperfiltration, the Munich Wistar Frömter rat. COX2 and PTGER2 were upregulated by FFSS. Our data thus support an autocrine/paracrine COX2/PGE 2 pathway in hPC linked to concerted EP2 and EP4 signaling.

          Related collections

          Most cited references 81

          • Record: found
          • Abstract: found
          • Article: not found

          Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.

           K Livak,  T Schmittgen (2001)
          The two most commonly used methods to analyze data from real-time, quantitative PCR experiments are absolute quantification and relative quantification. Absolute quantification determines the input copy number, usually by relating the PCR signal to a standard curve. Relative quantification relates the PCR signal of the target transcript in a treatment group to that of another sample such as an untreated control. The 2(-Delta Delta C(T)) method is a convenient way to analyze the relative changes in gene expression from real-time quantitative PCR experiments. The purpose of this report is to present the derivation, assumptions, and applications of the 2(-Delta Delta C(T)) method. In addition, we present the derivation and applications of two variations of the 2(-Delta Delta C(T)) method that may be useful in the analysis of real-time, quantitative PCR data. Copyright 2001 Elsevier Science (USA).
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Prostaglandins and leukotrienes: advances in eicosanoid biology.

             Cory Funk (2001)
            Prostaglandins and leukotrienes are potent eicosanoid lipid mediators derived from phospholipase-released arachidonic acid that are involved in numerous homeostatic biological functions and inflammation. They are generated by cyclooxygenase isozymes and 5-lipoxygenase, respectively, and their biosynthesis and actions are blocked by clinically relevant nonsteroidal anti-inflammatory drugs, the newer generation coxibs (selective inhibitors of cyclooxygenase-2), and leukotriene modifiers. The prime mode of prostaglandin and leukotriene action is through specific G protein-coupled receptors, many of which have been cloned recently, thus enabling specific receptor agonist and antagonist development. Important insights into the mechanisms of inflammatory responses, pain, and fever have been gleaned from our current understanding of eicosanoid biology.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Cell biology of the glomerular podocyte.

              Glomerular podocytes are highly specialized cells with a complex cytoarchitecture. Their most prominent features are interdigitated foot processes with filtration slits in between. These are bridged by the slit diaphragm, which plays a major role in establishing the selective permeability of the glomerular filtration barrier. Injury to podocytes leads to proteinuria, a hallmark of most glomerular diseases. New technical approaches have led to a considerable increase in our understanding of podocyte biology including protein inventory, composition and arrangement of the cytoskeleton, receptor equipment, and signaling pathways involved in the control of ultrafiltration. Moreover, disturbances of podocyte architecture resulting in the retraction of foot processes and proteinuria appear to be a common theme in the progression of acquired glomerular disease. In hereditary nephrotic syndromes identified over the last 2 years, all mutated gene products were localized in podocytes. This review integrates our recent physiological and molecular understanding of the role of podocytes during the maintenance and failure of the glomerular filtration barrier.
                Bookmark

                Author and article information

                Journal
                Cells
                Cells
                cells
                Cells
                MDPI
                2073-4409
                19 May 2020
                May 2020
                : 9
                : 5
                Affiliations
                [1 ]Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Clinical Pharmacology and Toxicology, Charitéplatz 1, 10117 Berlin, Germany; eva.mangelsen@ 123456charite.de (E.M.); angela-martina.schulz@ 123456charite.de (A.S.); reinhold.kreutz@ 123456charite.de (R.K.)
                [2 ]Lipidomix GmbH, Robert-Rössle-Str. 10, B55, 13125 Berlin, Germany; michael.rothe@ 123456lipidomix.de
                [3 ]Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Electrochemical Signaling in Development and Disease, Robert-Rössle-Str. 10, 13125 Berlin, Germany; Aikaterini.Kourpa@ 123456mdc-berlin.de (A.K.); Daniela.Panakova@ 123456mdc-berlin.de (D.P.)
                [4 ]DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Potsdamer Straße 58, 10785 Berlin, Germany
                Author notes
                [* ]Correspondence: juliane.bolbrinker@ 123456charite.de ; Tel.: +49-30-450-525-225
                Article
                cells-09-01256
                10.3390/cells9051256
                7290667
                32438662
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                Categories
                Article

                Comments

                Comment on this article