eprintid: 1514580 rev_number: 28 eprint_status: archive userid: 608 dir: disk0/01/51/45/80 datestamp: 2016-11-28 15:14:54 lastmod: 2022-01-10 00:32:41 status_changed: 2016-11-28 15:14:54 type: article metadata_visibility: show creators_name: Menzies, RI creators_name: Tam, FW creators_name: Unwin, RJ creators_name: Bailey, MA title: Purinergic signaling in kidney disease ispublished: pub divisions: UCL divisions: B02 divisions: C10 divisions: D17 keywords: ATP, P2X, P2Y, adenosine, inflammation, kidney, renal tubule, vasculature note: Copyright © 2016, International Society of Nephrology. Published by Elsevier Inc. All rights reserved. This manuscript version is made available under a Creative Commons Attribution Non-commercial Non-derivative 4.0 International license (CC BY-NC-ND 4.0). This license allows you to share, copy, distribute and transmit the work for personal and non-commercial use providing author and publisher attribution is clearly stated. Further details about CC BY licenses are available at http://creativecommons.org/ licenses/by/4.0. Access may be initially restricted by the publisher. abstract: Nucleotides are key subunits for nucleic acids and provide energy for intracellular metabolism. They can also be released from cells to act physiologically as extracellular messengers or pathologically as danger signals. Extracellular nucleotides stimulate membrane receptors in the P2 and P1 family. P2X are ATP-activated cation channels; P2Y and P1 are G-protein coupled receptors activated by ATP, ADP, UTP, and UDP in the case of P2 or adenosine for P1. Renal P2 receptors influence both vascular contractility and tubular function. Renal cells also express ectonucleotidases that rapidly hydrolyze extracellular nucleotides. These enzymes integrate this multireceptor purinergic-signaling complex by determining the nucleotide milieu to titrate receptor activation. Purinergic signaling also regulates immune cell function by modulating the synthesis and release of various cytokines such as IL1-β and IL-18 as part of inflammasome activation. Abnormal or excessive stimulation of this intricate paracrine system can be pro- or anti-inflammatory, and is also linked to necrosis and apoptosis. Kidney tissue injury causes a localized increase in ATP concentration, and sustained activation of P2 receptors can lead to renal glomerular, tubular, and vascular cell damage. Purinergic receptors also regulate the activity and proliferation of fibroblasts, promoting both inflammation and fibrosis in chronic disease. In this short review we summarize some of the recent findings related to purinergic signaling in the kidney. We focus predominantly on the P2X7 receptor, discussing why antagonists have so far disappointed in clinical trials and how advances in our understanding of purinergic signaling might help to reposition these compounds as potential treatments for renal disease. date: 2017-02 date_type: published official_url: http://doi.org/10.1016/j.kint.2016.08.029 oa_status: green full_text_type: other language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1157807 doi: 10.1016/j.kint.2016.08.029 pii: S0085-2538(16)30482-3 lyricists_name: Unwin, Robert lyricists_id: RJUNW23 actors_name: Unwin, Robert actors_name: Oliver-Styller, Sophie actors_id: RJUNW23 actors_id: SOLIV71 actors_role: owner actors_role: impersonator full_text_status: public publication: Kidney International volume: 91 number: 2 pagerange: 315-323 event_location: United States issn: 1523-1755 citation: Menzies, RI; Tam, FW; Unwin, RJ; Bailey, MA; (2017) Purinergic signaling in kidney disease. Kidney International , 91 (2) pp. 315-323. 10.1016/j.kint.2016.08.029 <https://doi.org/10.1016/j.kint.2016.08.029>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/1514580/1/KI%20Review%20Unwin%20et%20al%20ID%20KI-05-16-0752%20R1.pdf