Expression of type I collagen mRNA in glomeruli of rats with passive Heymann nephritis

In passive Heymann nephritis (PHN) glomeruli exhibit marked basement membrane expansion around subepithelial immune deposits but they fail to show any change in mRNA levels of type IV collagen, laminin or fibronectin by Northern and slot-blot analysis, or in the amount or distribution of type IV collagen or laminin by immunohistology for up to 12 weeks after disease onset. On the other hand, in situ hybridization (ISH) revealed the appearance of positive cells exhibiting mRNA for the alpha 1 chain of rat type I collagen two to three weeks after the onset of PHN in all glomeruli of all rats. Positive cells persisted for at least eight weeks. In many glomeruli, the location of the clusters of silver grains suggested that they were in visceral epithelial cells. In controls injected with normal sheep IgG, and in early PHN (< 11 days after sheep anti-Fx1A), glomeruli were negative but cells in the renal capsule and adventitia of vessels showed strong ISH and served as positive controls. RNAse pre-treatment and the "sense" probe gave appropriately negative results. RNA from PHN glomeruli contained an alpha 1 type I collagen transcript of the same size as that from rat fibroblasts. These results show that the evolution of glomerular basement membrane expansion in rat membranous nephropathy coincides with the induction of a matrix gene that is not normally expressed in glomerular cells. Further, they suggest that the intercalation of ectopically-expressed matrix molecules may contribute to the production of a disorganized basement membrane.