Department of Pediatrics, The First Affiliated Hospital of Henan University, Kaifeng, Henan, China.
Department of Emergency and Disaster Medical Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China.
Mediators Inflamm. 2021 Aug 18;2021:6104529. doi: 10.1155/2021/6104529. eCollection 2021.
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.
人们认为葡萄糖波动（GF）在肾损伤中起作用，并与糖尿病肾病（DN）的发展有关。但机制尚不清楚。近年来，有氧糖酵解已成为 DN 的一个热门话题。GF、有氧糖酵解和 DN 之间存在内在联系。姜黄素（Cur）是姜黄的主要姜黄素类化合物，具有肾脏功能的特定保护特性。Cur 还参与调节有氧糖酵解开关。在这项研究中，我们首先在波动高葡萄糖的条件下测量了 HEK-293 细胞模型中的有氧糖酵解水平，并评估了 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 引起的这种细胞毒性。我们发现 GF 增加了 HEK-293 细胞中的有氧糖酵解，Cur 对这种恶化表现出剂量依赖性的减弱作用。接下来，我们构建了一组先前报道可介导瓦伯格效应的 17 种 miRNA 和 8 种 lncRNA。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，而 Cur 可以防止这种下调。然后，我们计划探索 miR-489 在 GF 条件下 Cur 触发的瓦伯格效应衰减中的特征。我们的研究结果表明，Cur 通过上调 HEK-293 细胞中的 miR-489 来防止 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 miR-489/LDHA 轴在 HEK-293 细胞中防止 GF 触发的有氧糖酵解。总之，本研究表明，Cur 通过 miR-489/LDHA 轴在 HEK-293 细胞模型中防止 GF 触发的肾损伤，从而抑制有氧糖酵解。
