Author:
Zhao Junyi,Shi Jun,Shan Yun,Yu Manshu,Zhu Xiaolin,Zhu Yilin,Liu Li,Sheng Meixiao
Abstract
Abstract
Background
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.
Purpose
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).
Methods
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.
Results
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.
Conclusions
Asiaticoside inhibited the TGF-β1-induced MMT and ROS via Nrf2 activation, thus protecting the peritoneal membrane and preventing PF.
Funder
National Natural Science Foundation of China
Natural Science Foundation of Jiangsu Province
Leading Talent Project in Jiangsu Province
Summit Scholar Project in Jiangsu Province Hospital of Chinese Medicine
Publisher
Springer Science and Business Media LLC
Subject
Cell Biology,Molecular Biology,Biochemistry
Cited by
27 articles.
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