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 in vitro and in vivo. 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 vivo 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 in vitro and in vivo, 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.

中文翻译：

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miR-211 通过靶向 TGFβR2/TGF-β/SMAD3 通路减轻缺血/再灌注诱导的肾损伤。

MicroRNA-211（miR-211）与细胞凋亡密切相关，在缺血/再灌注（I/R）损伤中起重要作用。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，我们在体外和体内评估了 miR-211 在人肾小管上皮细胞中对缺氧复氧 (H/R) 刺激和 I/R 损伤的反应。结果表明，在进行 H/R 处理的人肾 (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。强化的 miR-211 表达降低了 H/R 诱导的 HK-2 细胞凋亡并增加了细胞活力，而靶向 miR-211 进一步增加了 H/R 诱导的 HK-2 细胞凋亡并降低了细胞活力。然而，通过靶向 TGFβR2 或在 miR-211 过表达细胞或 miR-211 过表达细胞中强制表达 TGFβR2，可以逆转 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。在小鼠体内，miR-211 过表达可改善生化和组织学肾损伤，减少 I/R 后小鼠的细胞凋亡。相反，miR-211 的下调促进了 I/R 后小鼠的组织学肾损伤和细胞凋亡。抑制 miR-211 或 miR-211 过表达可在体外和体内抑制 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 信号抑制细胞凋亡并减轻 H/R 或 I/R 后的肾损伤。所以，