Acute kidney injury (AKI) is highly prevalent among hospitalized patients and is associated with serious consequences with limited pharmacological treatment options. Pannexin 1 (Panx1) channel is a ubiquitously expressed nonselective membrane transport channel that efficiently effluxes ATP and plays a central role in the progression of inflammatory diseases. Animal models that target Panx1 through pharmacological inhibition or genetic deficiency have better outcomes in minimizing inflammation and associated pathology. Given the involvement of Panx1 at multiple steps of -inflammatory pathology, Panx1 could be a potential therapeutic target in the treatment of AKI. Further research is needed in elaborating the mechanisms and identifying Panx1-specific inhibitor molecules to better understand the role of Panx1 in AKI pathology arising due to diverse insults.

Keywords:
Acute kidney injury, Adenosine, ATP, Mitochondria, Pannexins, Purinergic signaling
1.
Pavkov ME, Harding JL, Burrows NR. Trends in Hospitalizations for Acute Kidney Injury - United States, 2000-2014.
MMWR Morb Mortal Wkly Rep
. 2018 Mar;67(10):289–93.
2.
Ostermann M, Cerdá J. The Burden of Acute Kidney Injury and Related Financial Issues.
Contrib Nephrol
. 2018;193:100–12.
3.
Panchin Y, Kelmanson I, Matz M, Lukyanov K, Usman N, Lukyanov S. A ubiquitous family of putative gap junction molecules.
Curr Biol
. 2000 Jun;10(13):R473–4.
4.
Penuela S, Gehi R, Laird DW. The biochemistry and function of pannexin channels.
Biochim Biophys Acta
. 2013 Jan;1828(1):15–22.
5.
Lohman AW, Billaud M, Straub AC, Johnstone SR, Best AK, Lee M, et al. Expression of pannexin isoforms in the systemic murine arterial network.
J Vasc Res
. 2012;49(5):405–16.
6.
Pelegrin P, Surprenant A. Pannexin-1 mediates large pore formation and interleukin-1β release by the ATP-gated P2X7 receptor.
EMBO J
. 2006 Nov;25(21):5071–82.
7.
Chekeni FB, Elliott MR, Sandilos JK, Walk SF, Kinchen JM, Lazarowski ER, et al. Pannexin 1 channels mediate ‘find-me’ signal release and membrane permeability during apoptosis.
Nature
. 2010 Oct;467(7317):863–7.
8.
D’hondt C, Ponsaerts R, De Smedt H, Vinken M, De Vuyst E, De Bock M, et al. Pannexin channels in ATP release and beyond: an unexpected rendezvous at the endoplasmic reticulum.
Cell Signal
. 2011 Feb;23(2):305–16.
9.
Penuela S, Simek J, Thompson RJ. Regulation of pannexin channels by post-translational modifications.
FEBS Lett
. 2014 Apr;588(8):1411–5.
10.
Lohman AW, Leskov IL, Butcher JT, Johnstone SR, Stokes TA, Begandt D, et al. Pannexin 1 channels regulate leukocyte emigration through the venous endothelium during acute inflammation.
Nat Commun
. 2015 Aug;6(1):7965.
11.
Ledderose C, Liu K, Kondo Y, Slubowski CJ, Dertnig T, Denicoló S, et al. Purinergic P2X4 receptors and mitochondrial ATP production regulate T cell migration.
J Clin Invest
. 2018 Aug;128(8):3583–94.
12.
Li L, Huang L, Ye H, Song SP, Bajwa A, Lee SJ, et al. Dendritic cells tolerized with adenosine A₂AR agonist attenuate acute kidney injury.
J Clin Invest
. 2012 Nov;122(11):3931–42.
13.
Kinsey GR, Huang L, Jaworska K, Khutsishvili K, Becker DA, Ye H, et al. Autocrine adenosine signaling promotes regulatory T cell-mediated renal protection.
J Am Soc Nephrol
. 2012 Sep;23(9):1528–37.
14.
Jankowski J, Perry HM, Medina CB, Huang L, Yao J, Bajwa A, et al. Epithelial and Endothelial Pannexin1 Channels Mediate AKI.
J Am Soc Nephrol
. 2018 Jul;29(7):1887–99.
15.
Chiu YH, Schappe MS, Desai BN, Bayliss DA. Revisiting multimodal activation and channel properties of Pannexin 1.
J Gen Physiol
. 2018 Jan;150(1):19–39.
© 2019 S. Karger AG, Basel
2019
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.