Department of Traditional Chinese Medicine, Renmin Hospital of Wuhan University, Wuhan 430060, China.
Department of Acupuncture and Moxibustion, Renmin Hospital of Wuhan University, Wuhan 430060, China.
Int Immunopharmacol. 2020 Aug;85:106620. doi: 10.1016/j.intimp.2020.106620. Epub 2020 Jun 5.
Rhein has protective effect on uric acid nephropathy (UAN). This article aims to demystify the mechanism of function of rhein in UAN. Mouse kidney epithelial cell line (TCMK-1) was incubated with uric acid (UA) to induce inflammatory injury. Then, the TCMK-1 cells were treated with rhein. The relationships among lincRNA-Cox2, miR-150-5p and STAT1 were evaluated by luciferase reporter assay. CCK8 and flow cytometry were performed to detect cell proliferation and apoptosis. The levels of IL-6, IL-1β and TNF-α were investigated by enzyme linked immunosorbent assay. Western blot and quantitative real-time PCR were performed to examine the expression of genes and proteins. We found that UA suppressed proliferation and enhanced apoptosis and the levels of IL-6, IL-1β and TNF-α of TCMK-1 cells, which was effectively improved by rhein treatment. Furthermore, lincRNA-Cox2 overexpression caused an increase of apoptosis and inflammatory factors in the rhein-treated TCMK-1 cells. LincRNA-Cox2 regulated STAT1 expression by sponging miR-150-5p. And lincRNA-Cox2 promoted apoptosis and inflammatory injury of TCMK-1 cells by regulating miR-150-5p/STAT1 axis. In summary, our studies demonstrate that rhein has a protective effect against UAN by inhibiting renal inflammatory injury via lincRNA-Cox2/miR-150-5p/STAT1 axis.
大黄酸对尿酸肾病（UAN）具有保护作用。本文旨在阐明大黄酸在 UAN 中的作用机制。将小鼠肾上皮细胞系（TCMK-1）与尿酸（UA）孵育以诱导炎症损伤。然后，用大黄酸处理 TCMK-1 细胞。通过荧光素酶报告基因测定评估 lincRNA-Cox2、miR-150-5p 和 STAT1 之间的关系。通过 CCK8 和流式细胞术检测细胞增殖和凋亡。通过酶联免疫吸附试验检测 IL-6、IL-1β 和 TNF-α 的水平。通过 Western blot 和定量实时 PCR 检测基因和蛋白的表达。我们发现 UA 抑制了 TCMK-1 细胞的增殖并增强了其凋亡和 IL-6、IL-1β 和 TNF-α 的水平，大黄酸处理可有效改善这种情况。此外，lincRNA-Cox2 的过表达导致大黄酸处理的 TCMK-1 细胞中凋亡和炎症因子增加。lincRNA-Cox2 通过海绵吸附 miR-150-5p 调节 STAT1 的表达。并且，lincRNA-Cox2 通过调节 miR-150-5p/STAT1 轴促进 TCMK-1 细胞的凋亡和炎症损伤。总之，我们的研究表明，大黄酸通过抑制 lincRNA-Cox2/miR-150-5p/STAT1 轴抑制肾炎症损伤对 UAN 具有保护作用。
