Type IV Collagen mRNA Expression in Human Membranous Nephropathy

ABSTRACT

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.