Department of Nephrology, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Qingpu 201700, Shanghai, P.R. China.
Aging (Albany NY). 2020 Nov 24;13(1):340-350. doi: 10.18632/aging.104152.
Acute kidney injury (AKI) is a complex renal disease. Long non-coding RNAs (lncRNAs) have frequently been associated with AKI. In the present study, we aimed to investigate the molecular mechanism(s) of LINC00052 in AKI. We found that LINC00052 expression was significantly decreased in AKI patient serum. In addition, in a hypoxic AKI cell model, LINC00052 expression was strongly elevated. In an I/R-triggered AKI rat model, the expression of TNF-α, IL-6 and IL-1β mRNA was strongly elevated. Moreover, we predicted miR-532-3p to be targeted by LINC00052 in AKI. Overexpression of LINC00052 increased hypoxia-induced inhibition of NRK-52E cell proliferation and reversed hypoxia-triggered apoptosis. Furthermore, we found that induction of TNF-α, IL-6 and IL-1β was repressed by overexpression of LINC00052. LINC00052 decreased hypoxia-induced ROS and MDA accumulation and increased SOD activity. Decreased levels of c-myc and cyclin D1 were observed in renal tissues of AKI rats. Lastly, Wnt/β-catenin signaling was inactivated in NRK-52E cells experiencing hypoxia, and LINC00052 upregulation reactivated Wnt/β-catenin signaling by sponging miR-532-3p. Taken together, these results suggest that LINC00052 ameliorates AKI by sponging miR-532-3p and activating Wnt signaling.
急性肾损伤（AKI）是一种复杂的肾脏疾病。长链非编码 RNA（lncRNA）经常与 AKI 相关。在本研究中，我们旨在研究 LINC00052 在 AKI 中的分子机制。我们发现 AKI 患者血清中 LINC00052 的表达显著降低。此外，在缺氧 AKI 细胞模型中，LINC00052 的表达强烈上调。在 I/R 触发的 AKI 大鼠模型中，TNF-α、IL-6 和 IL-1β mRNA 的表达强烈上调。此外，我们预测 LINC00052 是 AKI 中的 miR-532-3p 的靶标。LINC00052 的过表达增加了缺氧诱导的 NRK-52E 细胞增殖抑制，并逆转了缺氧触发的细胞凋亡。此外，我们发现 TNF-α、IL-6 和 IL-1β 的诱导被 LINC00052 的过表达抑制。LINC00052 降低了缺氧诱导的 ROS 和 MDA 积累，并增加了 SOD 活性。AKI 大鼠肾组织中观察到 c-myc 和 cyclin D1 的水平降低。最后，在经历缺氧的 NRK-52E 细胞中，Wnt/β-catenin 信号通路被失活，而 LINC00052 的上调通过海绵 miR-532-3p 重新激活 Wnt/β-catenin 信号通路。总之，这些结果表明 LINC00052 通过海绵 miR-532-3p 和激活 Wnt 信号通路来改善 AKI。
