title: Loss of endogenous thymosin β4accelerates glomerular disease.
abstract: Glomerular disease is characterized by morphologic changes in podocyte cells accompanied by inflammation and fibrosis. Thymosin β4regulates cell morphology, inflammation, and fibrosis in several organs and administration of exogenous thymosin β4improves animal models of unilateral ureteral obstruction and diabetic nephropathy. However, the role of endogenous thymosin β4in the kidney is unknown. We demonstrate that thymosin β4is expressed prominently in podocytes of developing and adult mouse glomeruli. Global loss of thymosin β4did not affect healthy glomeruli, but accelerated the severity of immune-mediated nephrotoxic nephritis with worse renal function, periglomerular inflammation, and fibrosis. Lack of thymosin β4in nephrotoxic nephritis led to the redistribution of podocytes from the glomerular tuft toward the Bowman capsule suggesting a role for thymosin β4in the migration of these cells. Thymosin β4knockdown 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 β4is a modifier of glomerular injury, likely having a protective role acting as a brake to slow disease progression.
authors: Developmental Biology and Cancer Programme, UCL Institute of Child Health, London, United Kingdom.
authors: Elisavet
authors: E
authors: Vasilopoulou
authors: Developmental Biology and Cancer Programme, UCL Institute of Child Health, London, United Kingdom.
authors: Maria
authors: M
authors: Kolatsi-Joannou
authors: Nephrological Center, Medical Clinic and Policlinic IV, University of Munich, Munich, Germany.
authors: Maja T
authors: MT
authors: Lindenmeyer
authors: EM Research Services, University of Newcastle, Newcastle upon Tyne, United Kingdom.
authors: Kathryn E
authors: KE
authors: White
authors: MRC Centre for Transplantation, King's College London, London, United Kingdom.
authors: Michael G
authors: MG
authors: Robson
authors: Nephrological Center, Medical Clinic and Policlinic IV, University of Munich, Munich, Germany.
authors: Clemens D
authors: CD
authors: Cohen
authors: Developmental Biology and Cancer Programme, UCL Institute of Child Health, London, United Kingdom.
authors: Neil J
authors: NJ
authors: Sebire
authors: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.
authors: Paul R
authors: PR
authors: Riley
authors: Developmental Biology and Cancer Programme, UCL Institute of Child Health, London, United Kingdom.
authors: Paul J
authors: PJ
authors: Winyard
authors: Developmental Biology and Cancer Programme, UCL Institute of Child Health, London, United Kingdom. Electronic address: d.long@ucl.ac.uk.
authors: David A
authors: DA
authors: Long
mesh_terms: D000818:Animals; D002465:Cell Movement; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D005355:Fibrosis; D005921:Glomerulonephritis / Q000378:metabolism* / Q000473:pathology; D007678:Kidney Glomerulus / Q000473:pathology; D008264:Macrophages; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050199:Podocytes / Q000378:metabolism*; D013947:Thymosin / Q000378:metabolism*; D000099201:Thymosin beta(4)
chemical_list: D013947:Thymosin; D000099201:Thymosin beta(4)
keywords: cytoskeleton; fibrosis; glomerulus; inflammation; podocyte