Peritoneal fibrosis (PF) is a frequent complication caused by peritoneal dialysis (PD). Peritoneal mesothelial cells (PMCs), the first barrier of the peritoneum, play an important role in maintaining structure and function in the peritoneum during PD. Mesothelial-mesenchymal transition (MMT) and oxidative stress of PMCs are two key processes of PF. To elucidate the efficacy and possible mechanism of asiaticoside inhibition of MMT and ROS generation in TGF-β1-induced PF in human peritoneal mesothelial cells (HPMCs). MMT and ROS generation of HPMCs were induced by TGF-β1. To explain the anti-MMT and antioxidant role of asiaticoside, varied doses of asiaticoside, oxygen radical scavenger (NAC), TGF-β receptor kinase inhibitor (LY2109761) and Nrf2 inhibitor (ML385) were used separately. Immunoblots were used to detect the expression of signaling associated proteins. DCFH-DA was used to detect the generation of ROS. Transwell migration assay and wound healing assay were used to verify the capacity of asiaticoside to inhibit MMT. Immunofluorescence assay was performed to observe the subcellular translocation of Nrf2 and expression of HO-1. Asiaticoside inhibited TGF-β1-induced MMT and suppressed Smad signaling in a dose-dependent manner. Migration and invasion activities of HPMCs were decreased by asiaticoside. Asiaticoside decreased TGF-β1-induced ROS, especially in a high dose (150 μM) for 6 h. Furthermore, ML385 partly abolished the inhibitory effect of asiaticoside on MMT, ROS and p-Smad2/3. Asiaticoside inhibited the TGF-β1-induced MMT and ROS via Nrf2 activation, thus protecting the peritoneal membrane and preventing PF.

中文翻译：

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Asiaticoside 通过人腹膜间皮细胞系 HMrSV5 中的 Nrf2/HO-1 信号通路抑制 TGF-β1 诱导的间皮-间质转化和氧化应激。

腹膜纤维化（PF）是腹膜透析（PD）引起的常见并发症。腹膜间皮细胞 (PMC) 是腹膜的第一道屏障，在 PD 期间在维持腹膜结构和功能方面发挥着重要作用。PMC 的间皮-间质转化 (MMT) 和氧化应激是 PF 的两个关键过程。阐明积雪草苷抑制人腹膜间皮细胞 (HPMCs) TGF-β1 诱导的 PF 中 MMT 和 ROS 生成的功效和可能机制。HPMCs的MMT和ROS生成是由TGF-β1诱导的。为了解释积雪草苷的抗 MMT 和抗氧化作用，分别使用不同剂量的积雪草苷、氧自由基清除剂 (NAC)、TGF-β 受体激酶抑制剂 (LY2109761) 和 Nrf2 抑制剂 (ML385)。免疫印迹用于检测信号相关蛋白的表达。DCFH-DA 用于检测 ROS 的产生。Transwell迁移试验和伤口愈合试验用于验证积雪草苷抑制MMT的能力。免疫荧光法观察Nrf2的亚细胞易位和HO-1的表达。Asiaticoside 以剂量依赖性方式抑制 TGF-β1 诱导的 MMT 并抑制 Smad 信号传导。积雪草苷降低了HPMCs的迁移和侵袭活性。Asiaticoside 降低 TGF-β1 诱导的 ROS，尤其是在高剂量 (150 μM) 下 6 小时。此外，ML385部分消除了积雪草苷对MMT、ROS和p-Smad2/3的抑制作用。Asiaticoside 通过 Nrf2 激活抑制 TGF-β1 诱导的 MMT 和 ROS，从而保护腹膜并预防 PF。