MicroRNAs (miRNAs) are reported to be involved in renal hypoxia/reoxygenation (H/R) damage. To investigate this further, human kidney (HK-2) cells were cultured, subjected to H/R and the function of miR-30a-5p and glutamate dehydrogenase 1 (GLUD1) was evaluated. The results showed that, miR-30-5p was downregulated and GLUD1 was upregulated in HK-2 cells exposed to H/R. The relationship between miR-30a-5p and GLUD1 was determined using dual luciferase assays. Primary HK-2 cells were cultured in H/R and transfected with negative control 1 (NC1), negative control 2 (NC2), mimic, inhibitor or GLUD1 siRNA plasmids. Reactive oxygen species (ROS) generation, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities, and the rate of apoptosis in HK-2 cells were assessed. The results showed that, miR-30a-5p mimic reduced the production of ROS in HK-2 cells treated with H/R, but increased the activity of SOD, CAT and GPx. In addition, miR-30a-5p mimic significantly decreased H/R-mediated apoptosis, decreased the expression of bax and activity of caspase-3 and enhanced the expression of bcl-2. However, miR-30a-5p inhibitor showed the opposite effect with regard to the degree of oxidative damage and apoptosis in H/R-induced HK-2 cells. Silencing GLUD1 rescued the influence of miR-30a-5p inhibitor on oxidative injury and apoptosis in HK-2 cells stimulated with H/R. These results demonstrated that under H/R conditions, miR-30a-5p can reduce oxidative stress in vitro by targeting GLUD1, which may be a novel therapeutic target for liver failure and worth further study.

Previous studies implicated the mammalian target of rapamycin (mTOR)/hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) pathway in renal fibrosis and found that curcumin could suppress the expression of mTOR. Therefore, the aim of the present study was to investigate the therapeutic effects of curcumin against chronic renal failure (CRF) in a rat model induced by 5/6 nephrectomy through inhibition of mTOR/HIF-1α/VEGF signaling. A total of 70 male Sprague-Dawley rats were divided into seven groups: a sham group, a CRF group, and five treatment groups. Except for the sham rats, all rats underwent 5/6 nephrectomy to induce CRF. The 5/6 nephrectomized rats received treatment with curcumin vehicle, everolimus vehicle, curcumin, everolimus, or the combination of curcumin and everolimus. Everolimus, a specific inhibitor of mTOR, was used as a positive control. At the end of treatment, blood biochemical indexes, proteinuria and the kidney index were detected. Moreover, histological change was examined by hematoxylin and eosin staining, and protein expression levels were detected by Western blotting. The blood biochemical indexes, proteinuria, and kidney index were increased in the CRF group as compared to the sham group, which was accompanied by marked activation of the mTOR/HIF-1α/VEGF pathway. However, curcumin, as well as everolimus, restored or ameliorated these changes. These results indicate that activation of the mTOR/HIF-1α/VEGF signaling pathway plays an important role in the occurrence and development of CRF, and that curcumin has renoprotective effects by blocking activation of this pathway.

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