Expression of Fas antigen and Bcl-2 in human glomerulonephritis

Abstract

To understand the regulatory mechanism of apoptosis in human glomerulonephritis, we examined the expression of Fas antigen (CD95) and Bcl-2 in five normal human kidney specimens and 80 tissues from patients with several types of glomerular diseases. These proteins were detected in glomeruli by immunofluorescence. The number of intraglomerular cells positive for Fas antigen was high in Henoch-Schönlein purpura nephritis and lupus nephritis, and that of Bcl-2-positive intraglomerular cells was high in lupus nephritis, focal glomerular sclerosis, and IgA nephritis. Dual-labeling and staining on serial sections indicated that mesangial cells and occasionally infiltrating leukocytes expressed Fas antigen and Bcl-2. In situ hybridization detected Bcl-2 mRNA in glomerular cells. Electron microscopy revealed apoptotic cells and apoptotic bodies in proliferated mesangial areas and within the glomerular capillaries. Fragmented DNA was detected in glomeruli by in situ nick end labeling, the data of which paralleled the number of Fas antigen-positive intraglomerular cells. In mesangial proliferative types of glomerulonephritis, the population of Bcl-2-positive intraglomerular cells, but not that of Fas antigen-positive cells, was significantly correlated with the number of proliferating cell nuclear antigen-positive glomerular cells, the grade of mesangial cell increase, and the magnitude of proteinuria. This study showed that Fas antigen and Bcl-2 are up-regulated in the glomeruli of several types of human renal diseases. Bcl-2 overexpression might play a role in the prolonged proliferation of mesangial cells and glomerular hypercellularity in glomerulonephritis.

Renal bcl-2/bax expression in childhood Henoch–Schönlein nephritis: prognostic importance?

“…Besides, ROM levels are under the control of the Bcl-2 gene product (20,21). The mainly tubular expression of bax and bcl-2 in our patients is in agreement with the literature (18,22). However, the variable biopsy timing in our study is a drawback and thus immunohistochemical findings may represent different apoptotic stages.…”

“…Thus, the balance between them is critical for the progression of glomerular diseases. Bcl-2 expression correlates with proliferation/activation of mesangial cells (4,18,19). However, bax expression correlates with mesangial matrix expansion and type-IV collagen deposition.…”

Activated Macrophages Direct Apoptosis and Suppress Mitosis of Mesangial Cells

“…Furthermore, we observed increased rat MC Fas protein following cytokine priming, in keeping with studies of human MC (21). This correlates with work showing that some human MC during acute glomerular disease have increased Fas protein (41). Together, these data indicate that at least some MC in vivo share phenotypic features with cultured MC primed with cytokines in vitro.…”

Role and regulation of apoptotic cell death in the kidney Y2K update

“…Increased expression of Fas, Bcl-2 and Bax has been observed within the glomerulus in human proliferative glomerulonephritis (71,72). However, Bcl2 positivity was limited to less than 2 cells/glomerulus and it could represent expression by infiltrating leukocytes (71).…”