Visceral Glomerular Epithelial Cell DNA Synthesis in Experimental and Human Membranous Disease

Abstract

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.