It has been considered that glucose fluctuation (GF) plays a role in renal injury and is related to diabetic nephropathy (DN) development. But the mechanism is still unclear. Aerobic glycolysis has become a topical issue in DN in recent years. There is an internal connection between GF, aerobic glycolysis, and DN. Curcumin (Cur) is a principal curcuminoid of turmeric and possesses specific protective properties in kidney functions. Cur also participates in the regulation of aerobic glycolysis switch. In this study, we first measured the levels of aerobic glycolysis and evaluated Cur’s inhibitory ability in a cell model of HEK-293 under the condition of oscillating high glucose. The results indicated that GF exacerbated inflammation injury, oxidative stress, and apoptosis in HEK-293 cell, while Cur alleviated this cytotoxicity induced by GF. We found that GF increased aerobic glycolysis in HEK-293 cells and Cur presented a dose-dependent weakening effect to this exacerbation. Next, we built a panel of 17 miRNAs and 8 lncRNAs that were previously reported to mediate the Warburg effect. Our RT-qPCR results indicated that GF reduced the miR-489 content in the HEK-293 cell model and Cur could prevent this downregulation. Then, we planned to explore the character of miR-489 in Cur-triggered attenuation of the Warburg effect under GF condition. Our findings presented that Cur prevented GF-triggered aerobic glycolysis by upregulating miR-489 in HEK-293 cells. Next, we choose the miR-489/LDHA axis for further investigation. We confirmed that Cur prevented GF-triggered aerobic glycolysis via the miR-489/LDHA axis in HEK-293 cells. In conclusion, this study presented that Cur prevented GF-triggered renal injury by restraining aerobic glycolysis via the miR-489/LDHA axis in the HEK-293 cell model.

中文翻译：

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姜黄素通过 miR-489/LDHA 通路抑制有氧糖酵解来拮抗葡萄糖波动引起的肾损伤

已经认为葡萄糖波动（GF）在肾损伤中起作用并且与糖尿病肾病（DN）的发展有关。但机制仍不清楚。近年来，有氧糖酵解已成为 DN 的热门话题。GF、有氧糖酵解和 DN 之间存在内在联系。姜黄素 (Cur) 是姜黄的主要类姜黄素，对肾功能具有特定的保护作用。Cur 还参与有氧糖酵解开关的调节。在这项研究中，我们首先测量了有氧糖酵解的水平，并在振荡高糖条件下的 HEK-293 细胞模型中评估了 Cur 的抑制能力。结果表明，GF加剧了HEK-293细胞的炎症损伤、氧化应激和细胞凋亡，而Cur减轻了GF诱导的这种细胞毒性。我们发现 GF 增加了 HEK-293 细胞的有氧糖酵解，并且 Cur 对这种恶化表现出剂量依赖性的减弱作用。接下来，我们构建了一个由 17 个 miRNA 和 8 个 lncRNA 组成的面板，这些先前被报道可介导 Warburg 效应。我们的 RT-qPCR 结果表明，GF 降低了 HEK-293 细胞模型中的 miR-489 含量，Cur 可以防止这种下调。然后，我们计划在 GF 条件下探索 miR-489 在 Cur 触发的 Warburg 效应衰减中的特性。我们的研究结果表明，Cur 通过上调 HEK-293 细胞中的 miR-489 来阻止 GF 触发的有氧糖酵解。接下来，我们选择 miR-489/LDHA 轴进行进一步研究。我们证实 Cur 通过 HEK-293 细胞中的 miR-489/LDHA 轴阻止 GF 触发的有氧糖酵解。综上所述，