ECM GENE-EXPRESSION AND ITS MODULATION BY INSULIN IN DIABETIC RATS

The steady-state levels of mRNA encoding for the alpha1(IV) collagen chain, laminin B1 and B2 chains, basement membrane HSPG, and alpha1(I) and alpha1(III) collagen chains were examined in rat glomeruli at 4, 12, and 24 wk after injection of STZ. The mRNA levels for the alpha1(IV) collagen chain, laminin B1 and B2 chains, and alpha1(I) and alpha1(III) collagen chains increased significantly with age in the STZ-induced diabetic rats before morphological thickening of basement membrane occurred. In contrast, the mRNA levels for HSPG decreased markedly 4 wk after STZ injection and then increased with age compared with those for control rats. The mRNA levels for these ECM components showed a continuous decline with age in controls. Treating the diabetic rats with insulin for 4 wk ameliorated the abnormally regulated ECM gene expression in the glomeruli. These data suggest that the abnormal regulation of ECM gene expression in the glomeruli may contribute to the expansion of mesangial matrix and basement membrane thickening in diabetic rats, and that hyperglycemia may play a role in the abnormal ECM gene expression.