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Upregulation of c-mip is closely related to podocyte dysfunction in membranous nephropathy.

Abstract : Membranous nephropathy is a glomerular disease typified by a nephrotic syndrome without infiltration of inflammatory cells or proliferation of resident cells. Although the cause of the disease is unknown, the primary pathology involves the generation of autoantibodies against antigen targets on the surface of podocytes. The mechanisms of nephrotic proteinuria, which reflect a profound podocyte dysfunction, remain unclear. We previously found a new gene, c-mip (c-maf-inducing protein), that was associated with the pathophysiology of idiopathic nephrotic syndrome. Here we found that c-mip was not detected in the glomeruli of rats with passive-type Heymann nephritis given a single dose of anti-megalin polyclonal antibody, yet immune complexes were readily present, but without triggering of proteinuria. Rats reinjected with anti-megalin develop heavy proteinuria a few days later, concomitant with c-mip overproduction in podocytes. This overexpression was associated with the downregulation of synaptopodin in patients with membranous nephropathy, rats with passive Heymann nephritis, and c-mip transgenic mice, while the abundance of death-associated protein kinase and integrin-linked kinase was increased. Cyclosporine treatment significantly reduced proteinuria in rats with passive Heymann nephritis, concomitant with downregulation of c-mip in podocytes. Thus, c-mip has an active role in the podocyte disorders of membranous nephropathy.
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Submitted on : Thursday, July 18, 2013 - 7:00:08 AM
Last modification on : Thursday, April 28, 2022 - 2:18:01 PM
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Kelhia Sendeyo, Vincent Audard, Shao-Yu Zhang, Qingfeng Fan, Khedidja Bouachi, et al.. Upregulation of c-mip is closely related to podocyte dysfunction in membranous nephropathy.. Kidney International, Nature Publishing Group, 2013, 83 (3), pp.414-25. ⟨10.1038/ki.2012.426⟩. ⟨inserm-00815234⟩



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