Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
Department of Clinical Lab, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
Bioengineered. 2020 Dec;11(1):547-557. doi: 10.1080/21655979.2020.1765501.
MicroRNA-211 (miR-211) is closely related to apoptosis and plays an important role in ischemia/reperfusion (I/R) injury. Whether miR-211 is involved in the protective effects in renal I/R injury is unknown. In this study, we evaluated the role of miR-211 in human tubular epithelial cells in response to hypoxia-reoxygenation (H/R) stimulation and I/R injury and . The results revealed that miR-211 was down-regulated and TGFβR2 was up-regulated in human kidney (HK-2) cells subjected to H/R. Luciferase reporter assay showed that TGFβR2 was a direct target of miR-211. Enforced miR-211 expression decreased H/R-induced HK-2 cell apoptosis and increased cell viability, and targeting miR-211 further increased H/R-induced HK-2 cell apoptosis and decreased cell viability. However, the effect of miR-211 was reversed by targeting TGFβR2 or enforced TGFβR2 expression in miR-211 overexpressing cells or miR-211 downexpressing cells. Moreover, we confirmed that miR-211 interacted with TGFβR2, and regulating TGF-β/SMAD3 signal. in mice, miR-211 overexpression ameliorates biochemical and histological kidney injury, reduces apoptosis in mice following I/R. On the contrary, miR-211 downexpressing promoted histological kidney injury and increased apoptosis in mice following I/R. Inhibition of miR-211 or miR-211 overexpression inhibited TGF-β/SMAD3 pathways or activated TGF-β/SMAD3 signal pathways and , which are critical for cell survival. Our findings suggested that miR-211 suppress apoptosis and relieve kidney injury following H/R or I/R via targeting TGFβR2/TGF-β/SMAD3 signals. Therefore, miR-211 may be as therapeutic potential for I/R- induced kidney injury.
微小 RNA-211（miR-211）与细胞凋亡密切相关，在缺血/再灌注（I/R）损伤中发挥重要作用。miR-211 是否参与肾 I/R 损伤的保护作用尚不清楚。在这项研究中，我们评估了 miR-211 在人肾小管上皮细胞对缺氧/复氧（H/R）刺激和 I/R 损伤的作用。结果表明，在接受 H/R 的人肾（HK-2）细胞中，miR-211 下调，TGFβR2 上调。荧光素酶报告基因检测表明，TGFβR2 是 miR-211 的直接靶标。强制表达 miR-211 可降低 H/R 诱导的 HK-2 细胞凋亡并增加细胞活力，而靶向 miR-211 进一步增加 H/R 诱导的 HK-2 细胞凋亡并降低细胞活力。然而，在 miR-211 过表达细胞或 miR-211 下调细胞中，靶向 TGFβR2 或强制表达 TGFβR2 可逆转 miR-211 的作用。此外，我们证实 miR-211 与 TGFβR2 相互作用，并调节 TGF-β/SMAD3 信号。在小鼠中，miR-211 过表达可改善 I/R 后肾脏的生化和组织学损伤，减少细胞凋亡。相反，miR-211 下调促进了 I/R 后小鼠的组织学肾脏损伤和细胞凋亡增加。miR-211 抑制或 miR-211 过表达抑制 TGF-β/SMAD3 通路或激活 TGF-β/SMAD3 信号通路，这对细胞存活至关重要。我们的研究结果表明，miR-211 通过靶向 TGFβR2/TGF-β/SMAD3 信号抑制 H/R 或 I/R 后的细胞凋亡并减轻肾脏损伤。因此，miR-211 可能具有治疗 I/R 诱导的肾脏损伤的潜力。
