Department of Urological Surgery, The Eighth Affiliated Hospital of Sun Yat-sen University (Shenzhen Futian), Shenzhen, 518033 Guangdong, China.
Department of Organ Transplantation, The Third Affiliated Hospital of Guangzhou Medical University, 3 Duobao Road, Liwan District, Guangzhou, 510150 Guangdong, China.
Dis Markers. 2022 Mar 17;2022:5845627. doi: 10.1155/2022/5845627. eCollection 2022.
Kruppel-like factor 4 (KLF4) owns the promising potential in treating kidney injury, which inevitably occurs during renal allograft. Given that, this research targets to unveil KLF4-oriented mechanism from microRNA-155-5p/ERBB receptor feedback inhibitor 1 (miR-155-5p/ERRFI1) axis in acute renal allograft injury. Mice were injected with miR-155-5p-related sequences before acute renal allograft modeling. Afterwards, serum inflammation, along with oxidative stress, renal tubular injury, and apoptosis in renal tissues were detected. HK-2 cells were processed by hypoxia/reoxygenation (H/R) and transfected with miR-155-5p- or ERRFI1-related sequences, after which cell proliferation and apoptosis were measured. KLF4, miR-155-5p, and ERRFI1 expressions and their interaction were tested. KLF4 and miR-155-5p levels were enhanced, and ERRFI1 level was repressed in mice after acute renal allograft and in H/R-treated HK-2 cells. KLF4 bound to the promoter of miR-155-5p. Depleting miR-155-5p reduced serum inflammation and attenuated oxidative stress, renal tubular injury, and apoptosis in mice with acute renal allograft injury. Downregulating miR-155-5p facilitated proliferation and repressed apoptosis of H/R-treated HK-2 cells. miR-155-5p targeted ERRFI1. Knocking down ERRFI1 antagonized the effects of downregulated miR-155-5p on acute renal allograft injury, as well as on H/R-treated HK-2 cell proliferation and apoptosis. A summary displays that silencing KLF4 suppresses miR-155-5p to attenuate acute renal allograft injury by upregulating ERRFI1, which provides a way to control acute renal allograft injury.
Kruppel 样因子 4（KLF4）在治疗肾移植过程中不可避免发生的肾损伤方面具有很大的应用潜力。因此，本研究旨在揭示 microRNA-155-5p/表皮生长因子受体反馈抑制剂 1（miR-155-5p/ERRFI1）轴上的 KLF4 导向机制在急性肾移植损伤中的作用。在建立急性肾移植模型前，给小鼠注射 miR-155-5p 相关序列。之后，检测血清炎症以及氧化应激、肾组织肾小管损伤和细胞凋亡情况。将 HK-2 细胞进行缺氧/复氧（H/R）处理，并转染 miR-155-5p 或 ERRFI1 相关序列，然后测量细胞增殖和凋亡情况。检测 KLF4、miR-155-5p 和 ERRFI1 的表达及其相互作用。结果显示，在急性肾移植后和 H/R 处理的 HK-2 细胞中，KLF4 和 miR-155-5p 的水平升高，而 ERRFI1 的水平降低。KLF4 结合在 miR-155-5p 的启动子上。miR-155-5p 耗竭可减少血清炎症并减轻急性肾移植损伤小鼠的氧化应激、肾小管损伤和细胞凋亡。下调 miR-155-5p 可促进 H/R 处理的 HK-2 细胞的增殖并抑制其凋亡。miR-155-5p 靶向 ERRFI1。敲低 ERRFI1 可拮抗下调 miR-155-5p 对急性肾移植损伤以及 H/R 处理的 HK-2 细胞增殖和凋亡的作用。研究结果表明，沉默 KLF4 通过上调 ERRFI1 抑制 miR-155-5p 可减轻急性肾移植损伤，为控制急性肾移植损伤提供了一种新的方法。
