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Ellagic acid alleviates high glucose-induced podocyte and renal epithelial cell apoptosis and hyperglycemia-induced renal injury by regulating NF-κB/miR-150-3p/BCL2


 Objective

Ellagic acid (EA) as a multi-target bioactive compound has been reported to improve diabetes-related complications, including diabetic nephropathy (DN). Herein, we plan to investigate the molecular mechanism underlying EA-mediated renal protection in diabetic mice.
Methods

Streptozotocin (STZ; 35 mg/kg successive injection for 5 times) was applied to establish DN model in mice. Normal or diabetic mice were administrated by EA (100 mg/kg/day) by intragastric administration for 8 weeks. In vitro diabetic cell model, podocytes and renal tubular epithelial cells (RTECs) were exposed to normal glucose (NG; 5 mM) or high glucose (HG; 30 mM).
Results

Our results demonstrated that EA treatment prevented HG-induced podocyte and RTEC apoptosis and growth inhibition by inhibiting NF-κB/miR-150-3p to activate BCL2 in vitro. In vivo diabetic model of mice, EA administration improved renal filtration function, tubular and glomerular injury, and interstitial fibrosis. More importantly, supplementation of EA also suppressed NF-κB/miR-150-3p activation and accelerated BCL2 expression in the kidney of diabetic mice. In another experiment, miR-150-3p antagomir as a potential gene therapeutic choice has been validated to rescue hyperglycemia-induced renal dysfunction in mouse model. Taken together, in vitro and in vivo experimental measurements corroborate that EA modulates NF-κB/miR-150-3p/BCL2 cascade signaling to attenuate renal damage in diabetic models.
Conclusion

Our findings revealed that EA modulated the suppression of NF-κB/miR-150-3p to activate BCL2 that contributed to prevent hyperglycemia-induced renal dysfunction. In addition, synthetic miR-150-3p antagomir or inhibitors could alleviate tubular injury and interstitial fibrosis, and prevent HG-induced podocyte and RTEC apoptosis.