Department of Intensive Care Unit, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, People's Republic of China.
Department of General Internal Medicine, Harbin Red Cross Center Hospital, Harbin, 150080, People's Republic of China.
Biochem Biophys Res Commun. 2021 Feb 12;540:1-7. doi: 10.1016/j.bbrc.2020.12.018. Epub 2021 Jan 8.
Our previous findings revealed that hsa_circ_0068,888 was markedly down-regulated in the plasma of patients with sepsis-associated acute kidney injury (AKI). However, its molecular mechanism in AKI remains unclear. Herein, we explored the role of hsa_circ_0068,888 in AKI. Human renal proximal tubular cell line HK-2 was stimulated with lipopolysaccharide (LPS) to mimic AKI in vitro. Decreased hsa_circ_0068,888 expression was observed in AKI cell model. The overexpression of hsa_circ_0068,888 significantly increased the viability of LPS-stimulated HK-2 cells, whereas hsa_circ_0068,888 downregulation showed the opposite effect. Furthermore, LPS triggered inflammatory response and oxidative stress, which was inhibited by hsa_circ_0068,888 overexpression and enhanced by hsa_circ_0068,888 down-regulation. Hsa_circ_0068,888 overexpression suppressed the activation of nuclear factor-κB (NF-κB) pathway triggered by LPS as evidenced by decreased p-p65 protein level and nuclear translocation of p65 in hsa_circ_0068,888 overexpressed cells. Additionally, we proved that hsa_circ_0068,888 targeted microRNA-21-5p (miR-21-5p). The expression of miR-21-5p was markedly increased and was negatively regulated by hsa_circ_0068,888 in LPS-stimulated HK-2 cells. Furthermore, we demonstrated that miR-21-5p overexpression reversed the effects on cell viability, inflammatory response, oxidative stress, and NF-κB pathway induced by hsa_circ_0068,888 overexpression in LPS-stimulated HK-2 cells. Overall, these results implied that hsa_circ_0068,888 shows a protective effect on AKI by sponging miR-21-5p. Hence, up-regulation of hsa_circ_0068,888 might be a potential strategy in treatment for AKI.
我们之前的研究结果表明，在脓毒症相关急性肾损伤（AKI）患者的血浆中，hsa_circ_0068,888 明显下调。然而，其在 AKI 中的分子机制尚不清楚。在此，我们探讨了 hsa_circ_0068,888 在 AKI 中的作用。用脂多糖（LPS）刺激人肾近端小管细胞系 HK-2 以在体外模拟 AKI。在 AKI 细胞模型中观察到 hsa_circ_0068,888 表达降低。hsa_circ_0068,888 的过表达显著增加 LPS 刺激的 HK-2 细胞的活力，而 hsa_circ_0068,888 的下调则表现出相反的效果。此外，LPS 触发炎症反应和氧化应激，而过表达 hsa_circ_0068,888 可抑制这些反应，下调 hsa_circ_0068,888 则增强这些反应。hsa_circ_0068,888 的过表达抑制了 LPS 触发的核因子-κB（NF-κB）通路的激活，这表现在过表达 hsa_circ_0068,888 的细胞中 p-p65 蛋白水平降低和 p65 核转位。此外，我们证明 hsa_circ_0068,888 靶向 microRNA-21-5p（miR-21-5p）。在 LPS 刺激的 HK-2 细胞中，miR-21-5p 的表达明显增加，并且受 hsa_circ_0068,888 的负调控。此外，我们证明 miR-21-5p 的过表达逆转了 LPS 刺激的 HK-2 细胞中 hsa_circ_0068,888 过表达对细胞活力、炎症反应、氧化应激和 NF-κB 通路的影响。总的来说，这些结果表明 hsa_circ_0068,888 通过海绵吸附 miR-21-5p 对 AKI 具有保护作用。因此，上调 hsa_circ_0068,888 可能是治疗 AKI 的一种潜在策略。
