Loss of endogenous thymosin βaccelerates glomerular disease.

Glomerular disease is characterized by morphologic changes in podocyte cells accompanied by inflammation and fibrosis. Thymosin βregulates cell morphology, inflammation, and fibrosis in several organs and administration of exogenous thymosin βimproves animal models of unilateral ureteral obstruction and diabetic nephropathy. However, the role of endogenous thymosin βin the kidney is unknown. We demonstrate that thymosin βis expressed prominently in podocytes of developing and adult mouse glomeruli. Global loss of thymosin βdid not affect healthy glomeruli, but accelerated the severity of immune-mediated nephrotoxic nephritis with worse renal function, periglomerular inflammation, and fibrosis. Lack of thymosin βin nephrotoxic nephritis led to the redistribution of podocytes from the glomerular tuft toward the Bowman capsule suggesting a role for thymosin βin the migration of these cells. Thymosin βknockdown 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 βis a modifier of glomerular injury, likely having a protective role acting as a brake to slow disease progression.