Analysis of alpha 1 (I) procollagen alpha 1 (IV) collagen, and beta-actin mRNA in glomerulus and cortex of rabbits with experimental anti-glomerular basement membrane disease. Evidence for early extraglomerular collagen biosynthesis

Abstract

Renal cortical and glomerular mRNA for alpha 1 (I) and alpha 1 (IV) collagen were measured by filter hybridization during experimental anti-glomerular basement membrane disease in the rabbit. The abundance of alpha 1 (IV) mRNA was 5 times greater in total RNA isolated from glomeruli as compared with whole renal cortex from normal rabbits. In contrast, there was no difference in the relative amounts of alpha 1 (I) procollagen mRNA in these two fractions. Four days after the administration of anti-glomerular basement membrane antisera, a time histologically characterized by glomerular inflammatory cell infiltration without crescent formation, beta-actin mRNA were increased 17-fold in glomeruli and 4-fold in whole renal cortex. Renal cortical mRNA for alpha 1 (I) and alpha 1 (IV) were increased 7-fold (p = 0.07) and 9-fold (p less than 0.05), respectively compared with normal rabbit kidney cortex. In contrast, there was no significant difference in the abundance of these mRNA in glomeruli at day 4. By day 7, cortical alpha 1 (I) and alpha 1 (IVP mRNA had increased 17- and 10-fold, respectively, and these transcripts had increased 13- and 7-fold in glomeruli. Cortical alpha 1 (I) mRNA remained elevated for 35 days. These data show that large changes in collagen mRNA levels occur early in this model of crescentic nephritis in the rabbit, and that extraglomerular collagen mRNA accumulates very rapidly when glomerular inflammation occurs. Extraglomerular collagen synthesis associated with intraglomerular inflammation may help to explain the common association of interstitial fibrosis with glomerulonephritis, particularly in the periglomerular area.