Asiaticoside Inhibits TGF-β1-induced Mesothelial-mesenchymal Transition and Oxidative Stress Via the Nrf2/HO-1 Signaling Pathway in the Human Peritoneal Mesothelial Cell Line HMrSV5

Overview

Journal Cell Mol Biol Lett

Publisher Biomed Central

Specialties Biochemistry
Cell Biology
Molecular Biology

Date 2020 Jun 10

PMID 32514269

Citations 17

Authors

Junyi Zhao

Jun Shi

Yun Shan

Manshu Yu

Xiaolin Zhu

Yilin Zhu

Li Liu

Meixiao Sheng

Affiliations

Soon will be listed here.

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.

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