Department of Emergency, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, China.
Eur Rev Med Pharmacol Sci. 2020 Dec;24(23):12258-12266. doi: 10.26355/eurrev_202012_24018.
The kidney is one of the most commonly damaged organs in sepsis. Acute kidney injury (AKI) induced by sepsis is a clinically dangerous disease with a high mortality rate. Therefore, it is particularly important to find a way to prevent and treat sepsis-induced AKI.
Human renal tubular epithelial cell line (HK-2) and 8-week-old C57BL/6 mice were used. Lipopolysaccharide (LPS) was used to induce HK-2 cell injury and mouse AKI. Lentiviruses overexpressing TRIM27 were constructed to increase TRIM27 expression in HK-2 cells. Then, the effects of TRIM27 on the inflammation and apoptosis of HK-2 cells were analyzed, and those of TRIM27 recombinant protein on AKI in mice was detected by immunohistochemical staining and Western blot.
It was found that TRIM27 overexpression reduced the expressions of inflammatory factors and signaling molecules in apoptosis-related pathways in HK-2 cells, but increased the ratio of Bcl-2 to Bax in HK-2 cells, indicating the anti-apoptotic effect of TRIM27. Toll-like receptor 4 (TLR4)/NF-κB signaling pathway is an important mechanism of LPS mediated renal injury, and TRIM27 overexpression in HK-2 cells significantly inhibited the activity of TLR4/NF-κB signaling pathway. In addition, AKI was significantly relieved in mice treated with TRIM27 recombinant.
TRIM27 exerts anti-inflammatory and anti-apoptotic effects by inhibiting the TLR4/NF-κB signaling pathway, which effectively alleviates LPS-induced HK-2 cell damage and mouse AKI.
肾脏是脓毒症中最常受损的器官之一。脓毒症引起的急性肾损伤（AKI）是一种临床危险疾病，死亡率高。因此，寻找预防和治疗脓毒症引起的 AKI 的方法尤为重要。
使用人肾小管上皮细胞系（HK-2）和 8 周龄 C57BL/6 小鼠。脂多糖（LPS）用于诱导 HK-2 细胞损伤和小鼠 AKI。构建过表达 TRIM27 的慢病毒以增加 HK-2 细胞中的 TRIM27 表达。然后，分析 TRIM27 对 HK-2 细胞炎症和凋亡的影响，并通过免疫组织化学染色和 Western blot 检测 TRIM27 重组蛋白对小鼠 AKI 的影响。
发现过表达 TRIM27 降低了 HK-2 细胞中凋亡相关途径中炎症因子和信号分子的表达，但增加了 HK-2 细胞中 Bcl-2 与 Bax 的比值，表明 TRIM27 具有抗凋亡作用。Toll 样受体 4（TLR4）/NF-κB 信号通路是 LPS 介导的肾损伤的重要机制，HK-2 细胞中 TRIM27 的过表达显著抑制 TLR4/NF-κB 信号通路的活性。此外，TRIM27 重组蛋白治疗明显缓解了小鼠的 AKI。
TRIM27 通过抑制 TLR4/NF-κB 信号通路发挥抗炎和抗凋亡作用，有效缓解 LPS 诱导的 HK-2 细胞损伤和小鼠 AKI。
