Helmholtz Gemeinschaft


Podocin inactivation in mature kidneys causes focal segmental glomerulosclerosis and nephrotic syndrome

Item Type:Article
Title:Podocin inactivation in mature kidneys causes focal segmental glomerulosclerosis and nephrotic syndrome
Creators Name:Mollet, G., Ratelade, J., Boyer, O., Muda, A.O., Morisset, L., Lavin, T.A., Kitzis, D., Dallman, M.J., Bugeon, L., Huebner, N., Gubler, M.C., Antignac, C. and Esquive, E.L.
Abstract:Podocin is a critical component of the glomerular slit diaphragm, and genetic mutations lead to both familial and sporadic forms of steroid-resistant nephrotic syndrome. In mice, constitutive absence of podocin leads to rapidly progressive renal disease characterized by mesangiolysis and/or mesangial sclerosis and nephrotic syndrome. Using established Cre-loxP technology, we inactivated podocin in the adult mouse kidney in a podocyte-specific manner. Progressive loss of podocin in the glomerulus recapitulated albuminuria, hypercholesterolemia, hypertension, and renal failure seen in nephrotic syndrome in humans. Lesions of FSGS appeared after 4 wk, with subsequent development of diffuse glomerulosclerosis and tubulointerstitial damage. Interestingly, conditional inactivation of podocin at birth resulted in a gradient of glomerular lesions, including mesangial proliferation, demonstrating a developmental stage dependence of renal histologic patterns of injury. The development of significant albuminuria in this model occurred only after early and focal foot process effacement had progressed to diffuse involvement, with complete absence of podocin immunolabeling at the slit diaphragm. Finally, we identified novel potential mediators and perturbed molecular pathways, including cellular proliferation, in the course of progression of renal disease leading to glomerulosclerosis, using global gene expression profiling.
Keywords:Gene Expression Profiling, Focal Segmental Glomerulosclerosis, Integrases, Intracellular Signaling Peptides and Proteins, Kidney Glomerulus, Kidney Tubules, Membrane Proteins, Nephrotic Syndrome, Podocytes, Animals, Mice
Source:Journal of the American Society of Nephrology
Publisher:American Society of Nephrology
Page Range:2181-2189
Date:27 August 2009
Official Publication:https://doi.org/10.1681/ASN.2009040379
PubMed:View item in PubMed

Repository Staff Only: item control page

Open Access
MDC Library