Changes in Expression of Syndecans and Heparan Sulfate Biosynthesis Enzymes in Short-Term Streptozotocin-Induced...

The aim of this study was to determine the temporal expression patterns of syndecan family members (SDC1, SDC2, SDC4) and heparan sulfate biosynthesis enzymes (NDST1, NDST2) in kidneys of diabetic rats and age-matched controls.

Male Sprague-Dawley rats received intraperitoneal streptozotocin (55 mg/kg; DM1 group) or citrate buffer (control group). Kidney samples were harvested after 2 weeks and 2 months and processed for immunofluorescence.

SDC1 showed significant temporal upregulation in controls that was abolished in diabetic animals. SDC2 exhibited high early expression in the control group with significant decline as the kidneys matured but remained elevated in diabetic kidneys at 2 months compared to controls. SDC4 showed no significant difference between groups, though an age-related decrease was observed in controls. NDST1 was significantly upregulated in diabetic rats at 2 weeks, followed by profound suppression at 2 months (p < 0.0001). NDST2 showed modest but significant early elevation in diabetic animals. Transcript-level analysis of two independent public datasets of streptozotocin-induced diabetic rat renal cortex reproduced the principal directional findings-an early increase in SDC1 and a progressive elevation of SDC2-while indicating post-transcriptional regulation of SDC4 and the early NDST response.

Diabetes disrupts normal temporal expression of syndecans and heparan sulfate biosynthesis enzymes in rat kidneys. Early compensatory upregulation of NDST1 and NDST2, followed by progressive NDST1 suppression, suggests a deteriorating heparan sulfate biosynthetic capacity, potentially contributing to the progression of diabetic nephropathy.