Abstract
Hepatic stellate cells (HSCs) migration, an important bioprocess, contributes to the development of liver fibrosis. Our previous studies have found the potent activity of dioscin against liver fibrosis by inhibiting HSCs proliferation, triggering the senescence and inducing apoptosis of activated HSCs, but the molecular mechanisms associated with cell migration were not clarified. In this work, iTRAQ (isobaric tags for relative and absolution quantitation)-based quantitative proteomics study was carried out, and a total of 1566 differentially expressed proteins with fold change ≥2.0 and p < 0.05 were identified in HSC-T6 cells treated by dioscin (5.0 μg/mL). Based on Gene Ontology classification, String and KEGG pathway assays, the effects of dioscin to inhibit cell migration via regulating SDC-4 were carried out. The results of wound-healing, cell migration and western blotting assays indicated that dioscin significantly inhibit HSC-T6 cell migration through SDC-4-dependent signal pathway by affecting the expression levels of Fn, PKCα, Src, FAK, and ERK1/2. Specific SDC-4 knockdown by shRNA also blocked HSC-T6 cell migration, and dioscin slightly enhanced the inhibiting effect. Taken together, the present work showed that SDC-4 played a crucial role on HSC-T6 cell adhesion and migration of dioscin against liver fibrosis, which may be one potent therapeutic target for fibrotic diseases.
Highlights
Hepatic stellate cells (HSCs) are a major cell type involved in liver tissue, which make up approximately 5–15% of the total liver cell population
The effect of dioscin on inhibiting the viability of HSC-T6 cells was investigated, and the results showed that the cell viability was significantly inhibited by dioscin with a dose-dependent manner (Supplementary Figure 1A)
The inhibitory effect of dioscin on fibrogenesis was evaluated, and the results showed that the mRNA levels COL3A1, COL1A1, and α-SMA were greatly reduced by the compound (Supplementary Figures 1B–D)
Summary
Hepatic stellate cells (HSCs) are a major cell type involved in liver tissue, which make up approximately 5–15% of the total liver cell population. HSCs can transfer to an activated, myofibroblast-like cells, lose their retinol stores, become proliferative and contractile, and migrate to the site of injury (Eng et al, 2000). Dioscin Inhibits HSC-T6 Cell Migration produce the regeneration of damaged hepatocytes (Rockey, 2001). Chronic activation of HSCs following persistent liver damage can result in promotion of fibrosis and alter the structure and functionality of the liver (Trautwein et al, 2015; Guo et al, 2017). The experimental and pharmacological approaches on inhibiting cell proliferation and migration of HSCs against liver fibrosis have been tested (Yang et al, 2017). HSCs migration is an important bioprocess for the development liver fibrosis (Zhao X. et al, 2017). Looking for potent drug to inhibit HSCs migration against liver fibrosis is important
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
