A study of HS-PG mRNA expression in the kidney of streptozotocin induced diabetic mice.

초록

Glomerular heparan sulfate proteoglycans (HSPG) are important in modulating mesangial cell proliferation, glomerular extracellular matrix assembly and glomerular permselectivity. Alterations of glomerular basement membrance HS-PG have been implicated as an early biochemical abnormality that may contribute to proteinuria indiabetes mellitus. This study was done to investigate the alterations of renal HS-PG gene expression with HS-PG cDNA probe in low dose streptozotocin (STZ)-induced diabetic mice, an experimental model of insulin dependent diabetes mellitus, with or without insulin treatment. Fifteen experimental mice (Group II) were given 40 mg/kg body wt daily of intraperitoneal (i.p.) STZ from day 1 to day 5; Fifteen experimental mice (Group III) were given STZ followed by daily 0.6 units of subcutaneous (s.c.) NPH injection from day 6 during the entire experimental period, and 9 control mice (Group I) received daily i.p. saline from day 1 to day 5. Control and STZ treated mice were checked for blood sugar levels at day 0, 14, 28, and 56, and were sacrificed at day 0, 28 and 56. mRNA from the whole kidney for HS-PG was quantitated by Northern blot analysis. At days 14, 28, and 56, significant increases in the level of blood sugar were found in the STZ mice (Groups II and III) compared to those in controls (Group I). At days 28 and 56, Northern blot analysis revealed decreased steady-state mRNA levels for HS-PG in the STZanimals (Groups II and III) compared to those in controls (Group I). Significant differences in Northern blot analysis at days 28 and 56 were not found between the STZ mice (Group II) and the STZ mice with insulin treatment (Group III). These results suggest that a reduction of renal HS-PG gene expression is an early important factor in the pathogenesis of diabetic nephropathy in STZ diabetic mice and insulin has no effects on amelioration of changes in renal HS-PG gene expression of mRNAextracted from the whole kidney in STZ diabetic mice.