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Loss of endogenous thymosin β4 accelerates glomerular disease

Lookup NU author(s): Dr Kathryn White

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Glomerular disease is characterized by morphologic changes in podocyte cells accompanied by inflammation and fibrosis. Thymosin beta(4) regulates cell morphology, inflammation, and fibrosis in several organs and administration of exogenous thymosin beta(4) improves animal models of unilateral ureteral obstruction and diabetic nephropathy. However, the role of endogenous thymosin beta(4) in the kidney is unknown. We demonstrate that thymosin beta(4) is expressed prominently in podocytes of developing and adult mouse glomeruli. Global loss of thymosin beta(4) did not affect healthy glomeruli, but accelerated the severity of immune-mediated nephrotoxic nephritis with worse renal function, periglomerular inflammation, and fibrosis. Lack of thymosin beta(4) in nephrotoxic nephritis led to the redistribution of podocytes from the glomerular tuft toward the Bowman capsule suggesting a role for thymosin beta(4) in the migration of these cells. Thymosin beta(4) knockdown in cultured podocytes also increased migration in a wound-healing assay, accompanied by F-actin rearrangement and increased RhoA activity. We propose that endogenous thymosin beta(4) is a modifier of glomerular injury, likely having a protective role acting as a brake to slow disease progression.


Publication metadata

Author(s): Vasilopoulou E, Kolatsi-Joannou M, Lindenmeyer MT, White KE, Robson MG, Cohen CD, Sebire NJ, Riley PR, Winyard PJ, Long DA

Publication type: Article

Publication status: Published

Journal: Kidney International

Year: 2016

Volume: 90

Issue: 5

Pages: 1056-1070

Print publication date: 01/11/2016

Online publication date: 26/08/2016

Acceptance date: 23/06/2016

Date deposited: 17/01/2017

ISSN (print): 0085-2538

ISSN (electronic): 1523-1755

Publisher: Elsevier

URL: http://dx.doi.org/10.1016/j.kint.2016.06.032

DOI: 10.1016/j.kint.2016.06.032


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Funding

Funder referenceFunder name
Else Kroner Fresenius Foundation
National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust
University College London
MR/J003638/1Medical Research Council
PDF8/2015KRUK
SF1/2008Kidney Research UK (KRUK)

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