Sci. Signal., 18 May 2010
Podocyte DisruptorPodocytes are cells with extensions known as foot processes that envelop the capillaries of the glomerulus in the kidney and prevent protein in the bloodstream from entering the urine. In individuals with idiopathic nephrotic syndrome, the podocytes lose their characteristic foot processes (a morphological alteration known as effacement) and protein appears in their urine (a symptom called proteinuria). Zhang et al. found that in some patients with various types of idiopathic nephrotic syndrome, the abundance of a protein known as c-mip was increased in podocytes. Transgenic mice that overexpressed c-mip developed proteinuria and effacement of foot processes. Biochemical analysis indicated that c-mip disrupted the interactions between proteins involved in regulating cytoskeletal reorganization in podocytes. Administration of the bacterial endotoxin lipopolysaccharide (LPS) induces proteinuria in mice, and the authors found that LPS-induced proteinuria was prevented by intravenous injection of a small interfering RNA directed against c-mip. Thus, c-mip may be a potential therapeutic target in the treatment of idiopathic nephrotic syndrome.
Citation: S. y. Zhang, M. Kamal, K. Dahan, A. Pawlak, V. Ory, D. Desvaux, V. Audard, M. Candelier, F. BenMohamed, M. Matignon, C. Christov, X. Decrouy, V. Bernard, G. Mangiapan, P. Lang, G. Guellaën, P. Ronco, D. Sahali, c-mip Impairs Podocyte Proximal Signaling and Induces Heavy Proteinuria. Sci. Signal. 3, ra39 (2010).
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