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Systemic gene therapy with thymosin β4 alleviates glomerular injury in mice

Mason, W; Jafree, Daniyal; Pomeranz, Gideon; Kolatsi-Joannou, Maria; Rottner, AK; Pacheco, S; Moulding, D; ... Vasilopoulou, E; + view all (2022) Systemic gene therapy with thymosin β4 alleviates glomerular injury in mice. Scientific Reports , Article 12172. 10.1038/s41598-022-16287-z. Green open access

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Abstract

Plasma ultrafiltration in the kidney occurs across glomerular capillaries, which are surrounded by epithelial cells called podocytes. Podocytes have a unique shape maintained by a complex cytoskeleton, which becomes disrupted in glomerular disease resulting in defective filtration and albuminuria. Lack of endogenous thymosin β4 (TB4), an actin sequestering peptide, exacerbates glomerular injury and disrupts the organisation of the podocyte actin cytoskeleton, however, the potential of exogenous TB4 therapy to improve podocyte injury is unknown. Here, we have used Adriamycin (ADR), a toxin which injures podocytes and damages the glomerular filtration barrier leading to albuminuria in mice. Through interrogating single-cell RNA-sequencing data of isolated glomeruli we demonstrate that ADR injury results in reduced levels of podocyte TB4. Administration of an adeno-associated viral vector encoding TB4 increased the circulating level of TB4 and prevented ADR-induced podocyte loss and albuminuria. ADR injury was associated with disorganisation of the podocyte actin cytoskeleton in vitro, which was ameliorated by treatment with exogenous TB4. Collectively, we propose that systemic gene therapy with TB4 prevents podocyte injury and maintains glomerular filtration via protection of the podocyte cytoskeleton thus presenting a novel treatment strategy for glomerular disease

Type: Article
Title: Systemic gene therapy with thymosin β4 alleviates glomerular injury in mice
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41598-022-16287-z
Publisher version: https://doi.org/10.1038/s41598-022-16287-z
Language: English
Additional information: © 2022 Springer Nature Limited. This article is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/).
Keywords: Cell biology, Kidney, Nephrology
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10152117
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