麝香草酚通过 NF-κB 介导的 RhoA/ROCK 信号通路的多效作用减轻 AGEs 诱导的足细胞损伤。

Thymol alleviates AGEs-induced podocyte injury by a pleiotropic effect via NF-κB-mediated by RhoA/ROCK signalling pathway.

机构信息

Department of Nephrology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.

Department of Biostatistics, WuXi Clinical Development Service (Shanghai) Co., Ltd, Shanghai, China.

出版信息

Cell Adh Migr. 2020 Dec;14(1):42-56. doi: 10.1080/19336918.2020.1721172.

Advanced glycation end products (AGE) are those of the most powerful pathogenic factors that related to diabetic complications. In our study, we investigated the beneficial effects of thymol on AGE induced cell injury and apoptosis in human podocytes (HPCs) and attempted to clarify its mechanisms. Our results revealed that stimulation with AGE could significantly activate RhoA/NF-κB pathway. Results showed thymol could markedly suppress inflammatory responses, cell apoptosis and disordered cytoskeleton. Also thymol restored the expression of podocin, restrained migration capacity. Western blot analysis indicated that it could restore the expression of RhoA, ROCK and vimentin, nephrin, podocin and p65 and IκBα phosphorylation. Moreover, si-RhoA also suppressed the expression of pro-inflammatory cytokines, ROCK, and vimentin and the phosphorylation of p65 and IκBα. In conclusion, thymol inhibits AGE-induced cell injury in HPCs by suppressing the RhoA-NF-κB pathway and may be apromising therapeutic agent.

晚期糖基化终产物（AGE）是与糖尿病并发症相关的最强大的致病因素之一。在我们的研究中，我们研究了麝香草酚对人足细胞（HPC）中 AGE 诱导的细胞损伤和细胞凋亡的有益作用，并试图阐明其机制。我们的结果表明，AGE 的刺激可显著激活 RhoA/NF-κB 通路。结果表明，麝香草酚可显著抑制炎症反应、细胞凋亡和细胞骨架紊乱。此外，麝香草酚还恢复了足突蛋白、抑制了迁移能力。Western blot 分析表明，它可以恢复 RhoA、ROCK 和波形蛋白、nephrin、podocin 和 p65 以及 IκBα 的磷酸化。此外，si-RhoA 还抑制了促炎细胞因子、ROCK 和波形蛋白以及 p65 和 IκBα 的磷酸化。总之，麝香草酚通过抑制 RhoA-NF-κB 通路抑制 AGE 诱导的 HPC 损伤，可能是一种有前途的治疗药物。