We aimed to evaluate the functions of long non-coding RNA taurine upregulated gene 1 (lncRNA TUG1) in renal ischemia-reperfusion (I/R) injury and identify the potential mechanisms. Pathological changes of renal tissues were examined using H&E staining after mimic renal I/R injury in vivo. The contents of serum renal functional parameters and inflammatory factors were measured. The expression of TUG1 and miR-449b-5p in renal tissues and HK-2 cells stimulated by I/R were detected. Then, the effects of TUG1 silencing on inflammation and apoptosis of cells were evaluated. Dual luciferase reporter assays were executed for determining the correlation between miR-449b-5p and TUG1, high mobility group box 1 (HMGB1), or matrix metalloproteinase 2 (MMP2). Subsequently, cells were co-transfected with miR-449b-5p mimic and pcDNA3.1 TUG1. The levels of inflammation, apoptosis, and the expression of HMGB1 and MMP2 were detected. The results revealed that renal tissues were obviously damaged after I/R accompanied by changes in renal functional markers and inflammatory factors. TUG1 was highly expressed whereas miR-449b-5p was lowly expressed. TUG1 silencing reduced the inflammation and apoptosis. Dual luciferase reporter assays confirmed that miR-449b-5p was a target of TUG1 as well as HMGB1 and MMP2 were direct targets of miR-449b-5p. Meanwhile, miR-449b-5p mimic presented the same results with TUG1 silencing, which were reversed after TUG1 overexpression. Moreover, MMP2 and HMGB1 expression was decreased after miR-449b-5p overexpression while that of was increased after TUG1 overexpression. These findings demonstrated that TUG1 silencing attenuates I/R-induced inflammation and apoptosis via targeting miR-449b-5p and regulating HMGB1 and MMP2 expression.

我们旨在评估长链非编码 RNA 牛磺酸上调基因 1 (lncRNA TUG1) 在肾缺血再灌注 (I/R) 损伤中的功能，并确定其潜在机制。体内模拟肾 I/R 损伤后使用 H&E 染色检查肾组织的病理变化. 测定血清肾功能参数和炎症因子的含量。检测 I/R 刺激后肾组织和 HK-2 细胞中 TUG1 和 miR-449b-5p 的表达。然后，评估了 TUG1 沉默对细胞炎症和凋亡的影响。执行双荧光素酶报告基因测定以确定 miR-449b-5p 和 TUG1、高迁移率组框 1 (HMGB1) 或基质金属蛋白酶 2 (MMP2) 之间的相关性。随后，用 miR-449b-5p 模拟物和 pcDNA3.1 TUG1 共转染细胞。检测炎症、细胞凋亡水平以及HMGB1和MMP2的表达。结果显示，I/R后肾组织明显受损，伴有肾功能标志物和炎症因子的变化。TUG1 高表达，而 miR-449b-5p 低表达。TUG1 沉默减少了炎症和细胞凋亡。双荧光素酶报告基因检测证实 miR-449b-5p 是 TUG1 的靶标，HMGB1 和 MMP2 是 miR-449b-5p 的直接靶标。同时，miR-449b-5p 模拟与 TUG1 沉默呈现相同的结果，在 TUG1 过表达后逆转。此外，miR-449b-5p 过表达后 MMP2 和 HMGB1 的表达降低，而 TUG1 过表达后 MMP2 和 HMGB1 的表达增加。这些发现表明，TUG1 沉默减弱了 I/R 诱导的炎症和细胞凋亡 在 TUG1 过表达后被逆转。此外，miR-449b-5p 过表达后 MMP2 和 HMGB1 的表达降低，而 TUG1 过表达后 MMP2 和 HMGB1 的表达增加。这些发现表明，TUG1 沉默减弱了 I/R 诱导的炎症和细胞凋亡 在 TUG1 过表达后被逆转。此外，miR-449b-5p 过表达后 MMP2 和 HMGB1 的表达降低，而 TUG1 过表达后 MMP2 和 HMGB1 的表达增加。这些发现表明，TUG1 沉默减弱了 I/R 诱导的炎症和细胞凋亡通过靶向 miR-449b-5p 并调节 HMGB1 和 MMP2 的表达。