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

The biosynthesis of basement membrane components in Engelbreth Helm Sw arm-bearing mice with or without streptozotocin-induced diabetes and t he effect of low-molecular-weight heparin derivatives (CY222, Sanofi R echerche/Institut Choay) on the relative rates of these synthetic acti vities were studied. In diabetic mice, the laminin mRNA level increase d, whereas type IV collagen mRNA decreased. In vivo treatment with hep arin fragments decreased the mRNA level of laminin to control values w ithout altering the mRNA level of collagen IV. Biosynthetic studies wi th radiolabeled precursors ([H-3]-proline for collagen and [S-35]-meth ionine for laminin) confirmed these results. Laminin protein biosynthe sis increased in diabetic mice. Treatment with CY222 corrected this al teration. Our results suggested an increased labeling of polymeric for ms of collagen IV in diabetic mice. In addition, we showed that biosyn thesis of acid-extractable collagen IV decreased in diabetic mice and that CY222 treatment corrected this disturbance. These experiments sug gest that low-molecular-weight heparin fragments CY222 can modulate th e biosynthesis of extracellular matrix macromolecules altered in diabe tic animals by different pathways, including pretranslational and post translational steps. Copyright (C) 1996 Elsevier Science Inc.