nephrin and Kidney-Neoplasms

Renal podocytes form the main filtration barrier possessing a unique phenotype maintained by proteins including podocalyxin and nephrin, the expression of which is suppressed in pathological conditions. We used an in vitro model of human glomerular epithelial cells (HGEC) to investigate the role of high glucose in dysregulating the podocytic epithelial phenotype and determined the time needed for this change to occur.. In our in vitro podocyte system changes indicating podocyte dedifferentiation in the prolonged presence of high glucose included loss of podocalyxin, nephrin and CD10/CALLA concomitant with upregulation of mesenchymal vimentin. Our study demonstrates for the first time that podocyte-specific markers undergo changes of expression at different time intervals, since glucose-mediated podocalyxin downregulation is a progressive process that precedes downregulation of nephrin expression. Finally we demonstrate that high glucose permanently impaired WT1 binding to the podocalyxin gene promoter region but did not affect WT1 binding on the nephrin gene promoter region.. The presence of high glucose induced a phenotypic conversion of podocytes resembling partial dedifferentiation. Our study demonstrates that dysregulation of the normal podocytic phenotype is an event differentially affecting the expression of function-specific podocytic markers, exhibiting downregulation of the epithelial marker CD10/CALLA and PC first, followed by stably downregulated nephrin. Furthermore, it is herein suggested that WT1 may not be directly involved with upregulation of previously reduced PC and nephrin expression.

Topics: Biomarkers; Cell Differentiation; Cells, Cultured; Down-Regulation; Glucose; Humans; In Vitro Techniques; Kidney Neoplasms; Membrane Proteins; Neprilysin; Phenotype; Podocytes; Sialoglycoproteins; Up-Regulation; Vimentin; Wilms Tumor

The aim of the study was to present our experience in treating children with genetic forms of nephrotic syndrome and diagnosing these diseases. We retrospectively reviewed the clinical data, mutational analyses, histopathological features, treatment modalities, and outcome of 26 consecutive children (20 families) suffering from congenital and/or steroid-resistant nephrotic syndrome who were assessed by genetic analysis. Ten out of 26 children (38%) had congenital nephrotic syndrome, 4/26 (15%) had infantile nephrotic syndrome, 10/26 (38%) had late-onset nephrotic syndrome, and 2/26 (9%) had asymptomatic proteinuria. We detected a mutation in 21/26 (81%) patients and in 15/20 (75%) families. NPHS1 mutation analyses were positive in 4/20 (20%), NPHS2 mutations in 4/20 (20%), WT1 mutations in 4/20 (20%), and PLCE1 mutations in 3/20 (15%) families. NPHS1 and PLCE1 mutations were solely found in patients with the earliest onset. The majority of patients, especially those with early onset of nephrotic syndrome, had serious adverse events related to the nephrotic status, and 19/26 (73%) reached end-stage renal failure at a median age of 27 months. Genetic forms of nephrotic syndrome comprise a heterogeneous group of genetic mutations. The progression toward end-stage renal failure is the rule but is highly variable between patients.

Topics: Adolescent; Age of Onset; Belgium; Child; Child, Preschool; Denys-Drash Syndrome; Female; Frasier Syndrome; Humans; Infant; Infant, Newborn; Intracellular Signaling Peptides and Proteins; Kidney Neoplasms; Male; Membrane Proteins; Nephrotic Syndrome; Phosphoinositide Phospholipase C; Proteinuria; Retrospective Studies; WT1 Proteins

To investigate the role of CD2-associated protein (CD2AP) and nephrin expression in the multilocular cystic renal cell carcinoma (MCRCC) METHODS: Seventy four specimens of renal lesions, including 29 cases of MCRCC, 32 case of clear cell renal cell carcinoma (CCRCC), and 13 cases of simple renal cyst (SRC), were collected during operation. Immunohistochemistry was used to detect the CD2AP expression. Five wax lumps from each of the 3 groups of specimen, totally 15, were randomly selected to undergo re-sectioning and immunohistochemistry so as to compare the levels of staining intensity and location of expression of CD2AP and nephrin in the same sections.. The expression of CD2AP in the MCRCC specimens was stronger than that in the CCRCC that was in turn stronger than that than that in the simple renal cyst (SRC) specimens. The epithelium lining the cysts in MCRCC was strongly positive in CD2AP compared to other parts. CCRCC showed a weak expression of CD2AP, while CD2AP was negative in the SRC specimens. The staining intensity and location of expression were completely identical for nephrin and CD2AP among the three types of tissue specimens.. The CD2AP expression is much stronger in MCRCC than in CCRCC and SRC. CD2AP may be used as a biomarker in differential diagnosis of MCRCC, CCRCC, and SRC. The identical expression of CD2AP and nephrin in MCRCC and their specific expression in podocytes are important hints for the mechanism of MCRCC.

Topics: Adaptor Proteins, Signal Transducing; Carcinoma, Renal Cell; Cytoskeletal Proteins; Humans; Immunohistochemistry; Kidney Neoplasms; Membrane Proteins

Several podocyte-related markers are organized to express in glomerular differentiation. However, whether expression of them is virtually synchronized and a reliable indicator of the state of differentiation is unknown. The present study investigated, by immunohistochemistry, the divergent expression of several podocyte markers in the improperly differentiated glomeruloid bodies from four cases of Wilms tumors. The glomeruloid bodies were classified into immature (IGB) or mature forms (MGB) based on morphology and epithelial features. Podocytes in IGB expressed WT1, synaptopodin, podocalyxin, and nephrin, and their expression was stronger in MGB. In contrast, Pax2 was strong in IGB and diminished in MGB. p27 was first expressed in MGB. The expression pattern in each molecule mimics normal glomerulogenesis. Podocytes in MGB showed persistent expression of bcl-2 and cytokeratin with synaptopodin, podocalyxin, and nephrin by serial section, a finding unusual for normal glomerulogenesis. Moreover, parietal cells in MGB also occasionally expressed these podocyte markers. The ultrastructure revealed that podocytes in MGB showed tight junctions without foot process formations, which indicated incomplete differentiation. These results suggest that a set of podocyte differentiation markers are occasionally diversely expressed, and raise the possibility that expression of these markers is insufficient to determine the state of terminal differentiation in podocytes.

Topics: Biomarkers, Tumor; Female; Humans; Infant; Keratins; Kidney Glomerulus; Kidney Neoplasms; Male; Membrane Proteins; Microfilament Proteins; Muscle Proteins; Proteins; Proto-Oncogene Proteins c-bcl-2; Sialoglycoproteins; Tight Junctions; Wilms Tumor; WT1 Proteins