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Visceral glomerular epithelial cell DNA synthesis in experimental and human membranous disease
E Bailey1, S J Harper, J H Pringle
1Department of Nephrology, Leicester General Hospital, UK.
Background:
Membranous nephropathy (MN) is a 'non-proliferative' glomerulonephritis. However, visceral glomerular epithelial cell (vGEC) proliferating cell nuclear antigen staining and increased glomerular histone mRNA in passive Heymann nephritis (PHN), suggest that vGECs may enter the cell cycle and undergo DNA synthesis. We used in situ hybridisation for histone mRNA, an S-phase specific marker, to investigate this possibility and identify the cellular origin of histone mRNA in PHN and MN.
Methods:
PHN was induced in 16 Sprague-Dawley rats. There were 8 saline/serum controls. 12 animals were sacrificed on days 5 and 10. Renal biopsies from 10 proteinuric cases with MN and matched controls were studied.
Results:
Day-5 Heymann animals demonstrated more S-phase cells/glomerulus than controls (0.53 +/- 0.09 vs. 0.195 +/- 0.045; p < 0.01). Glomerular S-phase cells were also increased in patients compared to controls (0.24 +/- 0.07 vs. 0.04 +/- 0.018; p < 0.03). In both experimental and human MN, the peripheral location and morphology of glomerular histone mRNA-positive cells was typical of vGECs.
Conclusion:
The results in PHN indicate that vGECs recently injured with antibody and complement enter into the cell cycle and undergo DNA synthesis. The S-phase vGECs in MN may indicate the persistence of immune injury. Whether or not this process leads to cell replication is open to question.
Insights
In membranous nephropathy (MN), injured visceral glomerular epithelial cells (vGECs) enter the cell cycle and synthesize DNA, suggesting persistent immune injury. Further research is needed to determine if this leads to cell replication.
Area of Science:
- Nephrology
- Cell Biology
- Immunopathology
Background:
- Membranous nephropathy (MN) is characterized as a non-proliferative glomerulonephritis.
- Evidence suggests visceral glomerular epithelial cells (vGECs) may proliferate in MN.
- Histone mRNA indicates DNA synthesis and cell cycle activity.
Purpose of the Study:
- To investigate vGEC cell cycle entry and DNA synthesis in passive Heymann nephritis (PHN) and human MN.
- To identify the cellular origin of histone mRNA in these conditions.
Main Methods:
- In situ hybridization for histone mRNA (an S-phase marker) was employed.
- Passive Heymann nephritis (PHN) was induced in rats.
- Renal biopsies from human MN cases and controls were analyzed.
Main Results:
- Rats with PHN showed increased S-phase cells in glomeruli compared to controls.
- Human MN patients exhibited elevated glomerular S-phase cells versus controls.
- Histone mRNA-positive cells in both experimental and human MN were located peripherally and resembled vGECs.
Conclusions:
- Injured vGECs in PHN enter the cell cycle and undergo DNA synthesis.
- Increased S-phase vGECs in MN may signify ongoing immune injury.
- The potential for vGEC replication in MN remains undetermined.