Expression of laminin and type IV collagen by basement membrane-producing EHS tumors in streptozotocin-induced diabetic mice: In Vivo modulation by low-molecular-weight heparin fragments

Abstract

The biosynthesis of basement membrane components in Engelbreth Holm Swarm-bearing mice with or without streptozotocin-induced diabetes and the effect of low-molecular-weight heparin derivatives (CY222, Sanofi Recherche/Institut Choay) on the relative rates of these synthetic activities were studied. In diabetic mice, the laminin mRNA level increased, whereas type IV collagen mRNA decreased. In vivo treatment with heparin fragments decreased the mRNA level of laminin to control values without altering the mRNA level of collagen IV. Biosynthetic studies with radiolabeled precursors ([ 3H]-proline for collagen and [ 35S]-methionine for laminin) confirmed these results. Laminin protein biosynthesis increased in diabetic mice. Treatment with CY222 corrected this alteration. Our results suggested an increased labeling of polymeric forms of collagen IV in diabetic mice. In addition, we showed that biosynthesis of acid-extractable collagen IV decreased in diabetic mice and that CY222 treatment corrected this disturbance. These experiments suggest that low-molecular-weight heparin fragments CY222 can modulate the biosynthesis of extracellular matrix macromolecules altered in diabetic animals by different pathways, including pretranslational and posttranslational steps.