Proto-Oncogene Expression in Human Glomerular Diseases

Abstract

The expression of the protein products and mRNA of c‐fos, c‐myc, p53, and c‐raf was examined in normal renal tissues and biopsy specimens from 73 patients with various glomerular diseases. Immunofluorescent staining showed that there were cell nuclei stained for c‐Fos, c‐Myc, and p53, and cytoplasm positive for c‐Raf, in the glomeruli of patients with proliferative types of glomerulonephritis, including IgA nephritis and lupus nephritis, and in patients with focal glomerular sclerosis. Glomerular expression of c‐fos and c‐myc mRNA was detected by in situ hybridization. The number of proto‐oncogene‐positive glomerular cells was significantly higher in lupus nephritis, IgA nephritis, and focal segmental sclerosis, as compared with minimal change nephrotic syndrome and normal specimens. In IgA nephritis, the population of glomerular cells positive for c‐Fos and c‐Myc and the grade of c‐Raf immunoreactivity were significantly correlated with the proportion of proliferating cell nuclear antigen (PCNA)‐positive glomerular cells, with histological grading of mesangial hypercellularity and matrix increase, and with the magnitude of proteinuria. These data indicate that proto‐oncogene expression is associated with mesangial proliferation and matrix expansion in proliferative types of glomerulonephritis and in focal glomerular sclerosis.

Expression of Fas, Bcl‐2 and p53 molecules in glomerulonephritis and their correlations with clinical and laboratory findings*

“…p53 positivity was also found to be correlated with increased BUN levels in patients in the present study. p53 expression seems to be associated with mesangial proliferation in various types of GN 37 . However, there were no significant differences between p53 positivity and the types of GN, clinical and laboratory (except with BUN) data in the present study.…”

“…p53 protein is increased by inflammatory mediators such as nitric oxide and superoxide that are expressed by mesangial cells during glomerular inflammation. In this way, p53 induces apoptosis and increasing expression of p53 correlates with mesangial proliferation and matrix expansion 35–39 …”

Coupled Induction of iNOS and p53 Upregulation in Renal Resident Cells May Be Linked with Apoptotic Activity in the Pathogenesis of Progressive IgA Nephropathy

“…Low to moderate p53 immunoreactivity in glomerular epithelium and endothelium was observed to peak in subgroup A (P Ͻ 0.05 versus all other groups, Figure 3 Given the well documented posttranslational mechanisms that govern p53 protein stability and the relatively low abundance of p53, MdM2, and c-Jun/c-Fos expression, as reported previously (17) and observed in the study presented here, we did not examine the gene expression patterns of these markers in renal tissue. Instead, we have focused on the modulation of these markers at the protein level in the context of their role in the immunopathogenesis of progressive IgAN.…”

Novel genes and variants associated with IgA nephropathy by co-segregating with the disease phenotypes in 10 IgAN families

“…MYC, although classified as an oncogene, has broad functionality. The evidence of its involvement in IgAN derives also from the observations that patients with IgAN nephropathy expressed more MYC RNA than did normal controls (Ebihara et al, 1991) and that higher activity of MYC was associated with the development of pathological lesions in various glomerulonephritis (Takemura et al, 1996;Qiu et al, 2004). Using our criteria, we did not select any MYC variants for examination in this study.…”