LncRNA H19 deficiency protects against the structural damage of glomerular endothelium in diabetic nephropathy via Akt/eNOS pathway.

This study aimed to investigate the functions of lncRNA H19 on glomerular endothelial structural damage of diabetic nephropathy (DN). Rats were fed a high sugar and fat high feed die, and intraperitoneally administrated with streptozotocin (30 mg/kg) to induce DN model. Meanwile, rat glomerular endothelial cells (rGEnCs) were treated with high a level of glucose （HG, 30 mM glucose）to induce structural damage. Our results showed that H19 level was drastically increased in diabetic glomeruli and high-glucose (HG)-stimulated rat glomerular endothelial cells (rGEnCs). Deficiency of H19 ameliorated microalbumin, creatinine, BUN, and histopathological alterations in diabetic rats. In addition, H19 deficiency significantly attenuated the damage of endothelial structure by upregulating the expression of junction proteins ZO-1 and Occludin, glycolcalyx protein Syndecan-1, and endothelial activation marker sVCAM-1 and sICAM-1 in diabetic rats. The results also showed that H19-siRNA alleviated glycocalyx shedding, tight junctions damage, and endothelial activation in HG-stimulated rGEnCs. Moreover, H19 deficiency significantly enhanced the expression of p-Akt and p-eNOS and NO concentration and . Pre-treatment with Akt inhibitor LY294002 abrogated these favourable effects mediated by H19 deficiency. These results indicate that H19 deficiency could mitigate the structural damage of glomerular endothelium in DN via activating Akt/eNOS pathway.