Recent progress in the pathogenesis of nephrotic proteinuria.
Nephrotic syndrome is caused by increased permeability of the glomerular capillary wall for proteins. The molecular pathogenesis of nephrotic proteinuria has still not been fully elucidated. Recently, mutations of several podocyte proteins have been identified as causes of familial nephrotic syndrome. This has led to progress in our understanding of the molecular structure of the slit diaphragm between podocyte foot processes and podocyte interaction with the glomerular basement membrane. Both the nephrin receptor complex at the slit diaphragm and integrin receptor that mediates binding of the podocyte to the glomerular basement membrane may mediate outside-inside signaling in the podocyte. Thus, the podocyte not only forms one of the barriers to protein permeability but also is a highly flexible dynamic system able to respond to injury. Recent progress in the knowledge of the structure and function of glomerular podocytes should result in the elucidation of the pathogenesis of nephrotic proteinuria in commonly acquired proteinuric diseases and should pave the way to new therapeutic approaches.
Tesar
Vladimír
V
Department of Nephrology, 1st School of Medicine and University Hospital, Charles University, Prague, Czech Republic. tesarv@lf1.cuni.cz
Zima
Tomás
T
D006801:Humans; D007668:Kidney / Q000473:pathology* / Q000503:physiopathology*; D008954:Models, Biological; D009404:Nephrotic Syndrome / Q000473:pathology* / Q000503:physiopathology*; D011507:Proteinuria / Q000473:pathology* / Q000503:physiopathology*