Vasilopoulou, Elisavet, Kolatsi-Joannou, Maria, Lindenmeyer, Maja T, White, Kathryn E, Robson, Michael G, Cohen, Clemens D, Sebire, Neil J, Riley, Paul R, Winyard, Paul J, Long, David A and others. (2016) Loss of endogenous thymosin β4 accelerates glomerular disease. Kidney international, 90 (5). pp. 1056-1070. ISSN 0085-2538. (doi:10.1016/j.kint.2016.06.032) (KAR id:63429)
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Official URL: http://dx.doi.org/10.1016/j.kint.2016.06.032 |
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 β4 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.
Item Type: | Article |
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DOI/Identification number: | 10.1016/j.kint.2016.06.032 |
Uncontrolled keywords: | cytoskeleton, fibrosis, glomerulus, inflammation, podocyte, medway school of pharmacy |
Subjects: | H Social Sciences |
Divisions: | Divisions > Division of Natural Sciences > Medway School of Pharmacy |
Funders: |
Kidney Research UK (https://ror.org/02kx7se86)
Medical Research Council (https://ror.org/03x94j517) |
Depositing User: | Elisavet Vasilopoulou |
Date Deposited: | 14 Sep 2017 16:37 UTC |
Last Modified: | 10 Jan 2024 11:15 UTC |
Resource URI: | https://kar.kent.ac.uk/id/eprint/63429 (The current URI for this page, for reference purposes) |
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