Ischemia-reperfusion injury in renal transplantation: 3 key signaling pathways in tubular epithelial cells

Smith, Stephanie F. ORCID:, Hosgood, Sarah A. and Nicholson, Michael L. (2019) Ischemia-reperfusion injury in renal transplantation: 3 key signaling pathways in tubular epithelial cells. Kidney International, 95 (1). pp. 50-56. ISSN 0085-2538

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Renal ischemia-reperfusion injury (IRI) is a significant clinical challenge faced by clinicians perioperatively in kidney transplantation. Recent work has demonstrated the key importance of transmembrane receptors in the injured tubular epithelial cell, most notably Toll-like receptors, activated by exogenous and endogenous ligands in response to external and internal stresses. Through sequential protein-protein interactions, the signal is relayed deep into the core physiological machinery of the cell, having numerous effects from upregulation of pro-inflammatory gene products through to modulating mitochondrial respiration. Inter-pathway cross talk facilitates a co-ordinated response at an individual cellular level, as well as modulating the surrounding tissue's microenvironment through close interactions with the endothelium and circulating leukocytes. Defining the underlying cellular cascades involved in IRI will assist the identification of novel interventional targets to attenuate IRI with the potential to improve transplantation outcomes. We present a focused review of 3 key cellular signalling pathways in the injured tubular epithelial cell that have been the focus of much research over the past 2 decades: toll-like receptors, sphingosine-1-phosphate receptors and hypoxia inducible factors. We provide a unique perspective on the potential clinical translations of this recent work in the transplant setting. This is particularly timely with the recent completion of phase I and ongoing phase 2 clinical trials of inhibitors targeting specific components of these signaling cascades.

Item Type: Article
Additional Information: Funding Information: The research was funded by the National Institute for Health Research Blood and Transplant Research Unit (NIHR BTRU) in Organ Donation and Transplantation at the University of Cambridge in collaboration with Newcastle University and in partnership with NHS Blood and Transplant (NHSBT). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, the Department of Health, or NHSBT. Publisher Copyright: © 2018 International Society of Nephrology
Uncontrolled Keywords: ischemia-reperfusion injury,tubular epithelial cells,nephrology ,/dk/atira/pure/subjectarea/asjc/2700/2727
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Depositing User: LivePure Connector
Date Deposited: 30 Oct 2021 00:47
Last Modified: 11 Dec 2023 01:20
DOI: 10.1016/j.kint.2018.10.009


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