Renal fibrosis results in the progressive renal dysfunction and leads to chronic kidney disease (CKD) and ultimately end-stage renal disease. Asiaticoside was reported to regulate synaptopodin, desmin, nephrin, and podocin levels in adriamycin-induced nephropathy of rats. In this study, we found out that asiaticoside inhibited renal fibrosis in vitro and in vivo. Additionally, miR-142-5p was upregulated in in vitro and in vivo models of CKD. MiR-142-5p promoted the levels of collagen-I, collagen-IV, and fibronectin proteins. Additionally, miR-142-5p overexpression partly rescued the protective effect of asiaticoside on renal fibrosis. Mechanistically, miR-142-5p inhibited ACTN4 levels by binding with its 3´untranslated region, and further reduced its translation. Treatment of asiaticoside decreased miR-142-5p levels and increased ACTN4 levels. Rescue assays revealed that ACTN4 overexpression partially rescued the effect of miR-142-5p on renal fibrosis. Asiaticoside mitigated renal fibrosis by regulating the miR-142-5p/ACTN4 axis. In conclusion, asiaticoside inhibits renal fibrosis by regulating the miR-142-5p/ACTN4 axis. This novel discovery suggested that asiaticoside may serve as a potential medicine for renal fibrosis improvement.

中文翻译：

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积雪草苷通过调节 miR-142-5p/ACTN4 轴抑制肾纤维化发展

肾纤维化导致进行性肾功能障碍，并导致慢性肾病 (CKD) 和最终终末期肾病。据报道，积雪草苷可调节阿霉素诱导的大鼠肾病中的突触蛋白、结蛋白、nephrin 和 podocin 水平。在这项研究中，我们发现积雪草苷在体外和体内均能抑制肾纤维化。此外，miR-142-5p 在 CKD 的体外和体内模型中被上调。MiR-142-5p 促进胶原蛋白-I、胶原蛋白-IV 和纤连蛋白的水平。此外，miR-142-5p 过表达部分挽救了积雪草苷对肾纤维化的保护作用。从机制上讲，miR-142-5p 通过与其 3' 非翻译区结合来抑制 ACTN4 水平，并进一步减少其翻译。积雪草苷的治疗降低了 miR-142-5p 水平并增加了 ACTN4 水平。拯救试验显示 ACTN4 过表达部分拯救了 miR-142-5p 对肾纤维化的影响。积雪草苷通过调节 miR-142-5p/ACTN4 轴减轻肾纤维化。总之，积雪草苷通过调节miR-142-5p/ACTN4轴抑制肾纤维化。这一新发现表明积雪草苷可能作为改善肾纤维化的潜在药物。