Loss of endogenous thymosin β accelerates glomerular disease
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Loss of endogenous thymosin β accelerates glomerular disease. / 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.
in: KIDNEY INT, Jahrgang 90, Nr. 5, 11.2016, S. 1056-1070.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Loss of endogenous thymosin β accelerates glomerular disease
AU - Vasilopoulou, Elisavet
AU - Kolatsi-Joannou, Maria
AU - Lindenmeyer, Maja T
AU - White, Kathryn E
AU - Robson, Michael G
AU - Cohen, Clemens D
AU - Sebire, Neil J
AU - Riley, Paul R
AU - Winyard, Paul J
AU - Long, David A
N1 - Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
PY - 2016/11
Y1 - 2016/11
N2 - Glomerular disease is characterized by morphologic changes in podocyte cells accompanied by inflammation and fibrosis. Thymosin β4 regulates cell morphology, inflammation, and fibrosis in several organs and administration of exogenous thymosin β4 improves animal models of unilateral ureteral obstruction and diabetic nephropathy. However, the role of endogenous thymosin β4 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 β4 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 β4 in nephrotoxic nephritis led to the redistribution of podocytes from the glomerular tuft toward the Bowman capsule suggesting a role for thymosin β4 in the migration of these cells. Thymosin β4 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 β4 is a modifier of glomerular injury, likely having a protective role acting as a brake to slow disease progression.
AB - Glomerular disease is characterized by morphologic changes in podocyte cells accompanied by inflammation and fibrosis. Thymosin β4 regulates cell morphology, inflammation, and fibrosis in several organs and administration of exogenous thymosin β4 improves animal models of unilateral ureteral obstruction and diabetic nephropathy. However, the role of endogenous thymosin β4 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 β4 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 β4 in nephrotoxic nephritis led to the redistribution of podocytes from the glomerular tuft toward the Bowman capsule suggesting a role for thymosin β4 in the migration of these cells. Thymosin β4 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 β4 is a modifier of glomerular injury, likely having a protective role acting as a brake to slow disease progression.
KW - Animals
KW - Cell Movement
KW - Cells, Cultured
KW - Cytoskeleton
KW - Fibrosis
KW - Glomerulonephritis
KW - Kidney Glomerulus
KW - Macrophages
KW - Male
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Podocytes
KW - Thymosin
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1016/j.kint.2016.06.032
DO - 10.1016/j.kint.2016.06.032
M3 - SCORING: Journal article
C2 - 27575556
VL - 90
SP - 1056
EP - 1070
JO - KIDNEY INT
JF - KIDNEY INT
SN - 0085-2538
IS - 5
ER -
