LncRNA MALAT1 Drives Diabetic Kidney Injury via Nrf2 Suppression in Glomerular Endothelium

Objective: To investigate the role of LncRNA MALAT1 in insulin resistance (IR) and and oxidative stress injury in glomerular endothelial cells (HGECs) under high glucose and insulin (HG/Ins) conditions, and to elucidate its regulatory mechanism involving the Nrf2 pathway. HGECs were exposed to 25 mM glucose and 100 nM insulin for 48 h to induce insulin resistance. MALAT1 was silenced by siRNA, with knockdown efficiency verified via qPCR. Groups included control, ML385, and SFN. Protein expression, ROS, apoptosis, and Nrf2 translocation were assessed by Western blot, flow cytometry, and immunofluorescence. Following IR induction in HGECs (25 mM glucose + 100 nM insulin, 48 h) and siRNA-mediated MALAT1 knockdown, effects on proteins, ROS, apoptosis, and Nrf2 translocation were assessed in control and modulator groups. Conclusion: MALAT1 exacerbates IR and oxidative stress-induced injury in HGECs by inhibiting Nrf2 nuclear translocation. Targeting the MALAT1-Nrf2 axis may serve as a novel strategy for diabetic nephropathy management.