Hindawi Publishing Corporation International Journal of Nephrology Volume 2012, Article ID 937623, 6 pages doi:10.1155/2012/937623 Review Article An Overview of Molecular Mechanism of Nephrotic Syndrome Juliana Reis Machado,1, 2 Laura Penna Rocha,1 Precil Diego Miranda de Menezes Neves,1 Eliaˆngela de Castro Coboˆ ,1 Marcos Vinı´cius Silva,2 Lu´ cio Roberto Castellano,3 Rosana Rosa Miranda Correˆa,1 and Marlene Antoˆ nia Reis1 1 Pathology Laboratory, Department of Biological Sciences, Federal University of Triaˆngulo Mineiro, 38025-180 Uberaba, MG, Brazil 2 Immunology Laboratory, Department of Biological Sciences, Federal University of Triaˆngulo Mineiro, 38025-180 Uberaba, MG, Brazil 3 Technical Health School of UFPB, Federal University of Para´ıba, 58051-900 Joa˜o Pessoa, PA, Brazil Correspondence should be addressed to Marlene Antoˆ nia Reis, mareis@patge.uftm.edu.br Received 8 May 2012; Revised 20 June 2012; Accepted 20 June 2012 Academic Editor: Omran Bakoush Copyright © 2012 Juliana Reis Machado et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Podocytopathies (minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS)) together with membranous nephropathy are the main causes of nephrotic syndrome. Some changes on the expression of nephrin, podocin, TGF-β, and slit diaphragm components as well as transcription factors and transmembrane proteins have been demonstrated in podocytopathies. Considering the pathogenesis of proteinuria, some elucidations have been directed towards the involvement of epithelial- mesenchymal transition. Moreover, the usefulness of some markers such as TGF-β1, nephrin, synaptopodin, dystroglycans, and malondialdehyde have been determined in the diﬀerentiation between MCD and FSGS. Experimental models and human samples indicated an essential role of autoantibodies in membranous glomerulonephritis, kidney damage, and proteinuria events. Megalin and phospholipase-A2-receptor have been described as antigens responsible for the formation of the subepithelial immune complexes and renal disease occurrence. In addition, the complement system seems to play a key role in basal membrane damage and in the development of proteinuria in membranous nephropathy. This paper focuses on the common molecular changes involved in the development of nephrotic proteinuria. 1. Introduction A variety of primary and systemic kidney diseases, trigger an excessive protein loss in the urine [1]. Diseases that progress to nephrotic syndrome are grouped into three categories: antibody-mediated diseases (e.g., lupus, membranoprolifer- ative glomerulonephritis, and membranous nephropathy); metabolic disorders (e.g., diabetes, amyloidosis, and Fabry disease) and podocytopathies [2, 3]. The main primary glomerulopathies that course with proteinuria are podocy- topathies (minimal change disease and focal segmental glomerulosclerosis), and membranous nephropathy. The podocytopathies are characterized by changes in podocytes. These changes may be at the structural or molecular levels, and some proteins have been shown as a pivot of renal injury and proteinuria development [4]. 2. Podocytopathies Podocyte dysfunction may have idiopathic, genetic, or reac- tive etiologies. The latter involves response to various insults, including mechanical stress, medications, toxins, viral infec- tions, and as yet unidentiﬁed circulating proteins [5]. focal adhesion kinase (FAK) plays an important role in the foot process eﬀacement commonly seen in podocytopathies [6, 7]. Focal segmental glomerulosclerosis (FSGS) involves changes in the slit membrane [8, 9] as well as in the cytoskele- ton and cell stress [8–10]. Furthermore, FSGS may occur due to a collapse of the capillary loop, which could be HIV-1 associated [11]. Mutations in WT1 gene can also cause Denys-Drash syndrome [12]. Alterations in podocyte proteins or mutations in their coding gene play an important