Hyperoside Protects HK-2 Cells Against High Glucose-Induced Apoptosis and Inflammation via the miR-499a-5p/NRIP1 Pathway

Abstract

Hyperoside, a flavonol glycoside, is derived from plants of the genera Hypericum and Crataegus. Recent studies have indicated the anti-apoptotic and anti-inflammatory roles of hyperoside. The present study was designed to measure the effects of hyperoside on high glucose (HG)-treated HK-2 cells. HK-2 is a human papillomavirus 16 transformed cell line and can be used as a model for normal tubular cell. Cell apoptosis was examined by TUNEL assays and flow cytometry analysis. Inflammatory response was detected by Enzyme linked immunosorbent assay kits. Western blotting was applied to detect protein levels of apoptosis-related genes and inflammatory cytokines. Mechanistical assays including luciferase reporter and RNA pull down assays were applied to detect the binding relationship between molecules. We identified that hyperoside protected HK-2 cells against HG-induced apoptosis and inflammation. Moreover, miR-499a-5p was upregulated by hyperoside in a dose dependent manner. MiR-499a-5p inhibition rescued the suppressive effects of hyperoside on apoptosis and inflammation of HG-treated HK-2 cells. Furthermore, miR-499a-5p targeted NRIP1 to inhibit its mRNA expression, and further suppressed its translation. NRIP1 was downregulated by hyperoside in a dose dependent manner. Finally, rescue assays indicated that miR-499a-5p inhibition rescued the protective effects of hyperoside on apoptosis and inflammatory response of HK-2 cells by NRIP1. In conclusion, our findings revealed that hyperoside alleviates HG-induced apoptosis and inflammatory response of HK-2 cells by the miR-499a-5p/NRIP1 axis.

LncRNA LINC01018 Screens Type 2 Diabetes Mellitus and Regulates β Cell Function Through Modulating miR-499a-5p

“…miR-499a-5p has also been illustrated to play roles in the biological processes of various cells, such as the proliferation, differentiation, and metastasis of tumor cells [20,21,28,29]. Additionally, miR-499a-5p was also revealed to regulate the resistance of pancreatic cancer cells to chemotherapy and mediate the protective effect of hyperoside on high glucose-induced apoptosis of tubular cells [19,30]. In the present study, miR-499a-5p was observed to reverse the protective effect of LINC01018 on high glucose-induced pancreatic β cell.…”

“…The interaction between LINC01018 and miR-499a-5p was also predicted by the online software with several binding sites. Moreover, miR-499a-5p was reported to mediate the protective effect of hyperoside on high glucose-induced human tubule epithelial cell apoptosis 19 . miR-499a-5p could also regulate cell differentiation of mesenchymal stem cells and osteosarcoma cells 20 21 .…”

Hyperoside as a Potential Natural Product Targeting Oxidative Stress in Liver Diseases

“…In addition, Hyp treatment (8, 65, and 500 mg/kg) for 38 weeks induced no abnormal reactions in symptoms, blood tests, and histological examination in Beagle dogs, and mild toxicity of the kidney and liver was negligible and reversible [ 98 ]. Other teams found that Hyp can contribute to the alleviation of renal cellular aging and injury in NRK-52E cells and rats exposed to D-galactose [ 99 ] as well as the protection of HK-2 (human renal proximal tubule cells) from high-glucose-induced apoptosis and inflammation [ 100 ].…”

NRIP1 aggravates lung injury caused by Pseudomonas aeruginosa in mice by increasing PIAS1 ubiquitination

“…In macrophages, NRIP1 can promote the activation of NF-κB and upregulate the expression of genes involved in the inflammatory response [ 4 ]. In high glucose treated HK-2 cells, Hyperoside downregulated the protein expression of NRIP1 dose-dependently, and reduced apoptosis and inflammatory response [ 5 ]. Another study showed that overexpression of NRIP1 induced proinflammatory cytokine release in cardiomyocytes, which could be reversed by p65 NF-κB inactivation.…”