Human membranous nephropathy (MN) is morphologically characterized by subepithelial immune complex deposits and progressive thickening of glomerular basement membranes (GBM). Studies have suggested that the enhanced secretion of classical and novel type IV collagen chains in MN contributes to spike formation and the novel type IV collagen chain is particularly related to thickening of GBM. It is unclear whether the increased accumulation of extracellular matrix (ECM) proteins in GBM is due to the increased mRNA expression for type IV collagen in glomerular visceral epithelial cells (GECs).
To answer this question, we analyzed seven renal biopsies of patients with idiopathic MN using in situ hybridization. In MN, the number of GECs expressing mRNA for alpha1(IV) collagen was 2.82+/-1.80/glomerular cross section (gcs), and the number expressing mRNA for alpha4(IV) collagen was 8.42+/-2.85/gcs. The number of GECs expressing mRNA for alpha4(IV) collagen was significantly larger than that of alpha1(IV) collagen mRNA.
The expression of mRNA for these ECM proteins in normal controls was negligible. These results suggest that subepithelial immune complexes stimulate the gene expression of alpha1(IV) collagen and alpha4(IV) collagen in glomerular GECs which, in turn, increase the secretion of ECM proteins and contribute to the thickening of GBM in MN.
BACKGROUND The natural history of idiopathic membranous nephropathy (IMN) is heterogeneous with some patients showing spontaneous remission while others show a progressive course leading to end-stage renal failure. We tried to assess quantitatively alpha-smooth muscle actin (alpha-SMA) and vimentin expression as markers to predict the outcome of membranous nephropathy. METHODS This study included 24 patients with biopsy proven IMN. We measured the volume of the positive area for alpha-SMA and vimentin within the glomeruli and compared the results with 5 patients in the normal control group. We evaluated glomerular alpha-SMA and vimentin expression in correlation with BUN and serum creatinine level at the time of diagnosis and after treatment. RESULTS Glomerular alpha-SMA and vimentin in IMN were higher than in the control group. Glomerular alpha-SMA was significantly higher in progressive IMN than in non-progressive IMN. The glomerular alpha-SMA was sifnificantly correlated with BUN and serum creatinine at last follow-up (p<0.05), but there was no statistically significant correlation at diagnosis. The glomerular vimentin was not different between progressive and non-progressive groups. CONCLUSION These data suggest that the expression of glomerular alpha-SMA may be a useful prognostic indicator and may be able to differentiate between patients with membranous nephropathy who respond well to treatment and those who continue to progress.