ABSTRACT

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.

摘要

晚期糖基化终末产物（AGE）是与糖尿病并发症相关的最有力的致病因素。在我们的研究中，我们调查了百里酚对AGE诱导的人足细胞（HPC）细胞损伤和凋亡的有益作用，并试图阐明其机制。我们的结果表明，AGE刺激可以显着激活RhoA /NF-κB通路。结果显示百里酚可显着抑制炎症反应，细胞凋亡和细胞骨架紊乱。百里酚还恢复了Podocin的表达，限制了迁移能力。Western blot分析表明它可以恢复RhoA，ROCK和波形蛋白，nephrin，podocin，p65和IκBα的磷酸化。此外，si-RhoA还抑制促炎细胞因子ROCK，和波形蛋白以及p65和IκBα的磷酸化。总之，百里香酚通过抑制RhoA-NF-κB途径抑制AGE诱导的HPC细胞损伤，可能是有希望的治疗剂。