Schisandrin B inhibits TGF-β1-induced epithelial-mesenchymal transition in human A549 cells through epigenetic silencing of ZEB1

Abstract

Purpose/Aim: More and more evidences suggest that airway remodeling of fibrotic lung diseases may be associated with epithelial-mesenchymal transition (EMT) of human A549 cells induced by transforming growth factor (TGF)-β1. Schisandrin B (Sch B) is the highest content of dibenzocyclooctadiene lignans in Schisandra chinensis. In this study, we assessed the inhibitory influences of Sch B on TGF-β1-stimulated EMT in human A549 cells. Materials and Methods: The influences of Sch B on cell viability, invasion and metastasis in TGF-β1-induced human A549 cells were detected by MTT, wound healing and transwell invasion assays. The expression levels of α-SMA, E-cadherin, ZEB1 and Twist1 were examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot. The enrichment of H3K4me3 and H3K9me3 at the ZEB1 promoter was determined by ChIP analysis. Results: Experimental results showed that Sch B increased the expression of the epithelial phenotype marker E-cadherin and inhibited the expression of the mesenchymal phenotype marker α-SMA during EMT induced by TGF-β1. The enhancement in invasion and migration of TGF-β1-induced A549 cells was inhibited by Sch B. Sch B also repressed the expression of ZEB1 transcription factor in EMT, by increasing the enrichment of H3K9me3 at the ZEB1 promoter to repress its transcription while the expression of the Twist1 transcription factor was unaffected. Conclusions: Our data suggest that Sch B can prevent TGF-β1-stimulated EMT in A549 cells through epigenetic silencing of ZEB1, which may be clinically related to the efficient treatment of EMT-associated fibrotic diseases.

Keywords:

• Schisandrin B
• epithelial-mesenchymal transition
• human A549 cells
• epigenetic modifications
• ZEB1

Declaration of interest

The authors declare no competing financial interests.

Additional information

Funding

This work was supported by grants from the National Science Foundation of Jilin Province Scientific Technology Development Project (20160101234JC), the Student's Training Program for Innovation and Entrepreneurship of Jilin Province (201811923144), Project of innovation plan for graduate students of Beihua University(201841), the Medical and Health Industry Development Special Fundation of Jilin Province Scientific Technology Development Project (20170311058YY) and Jilin Pharmaceutical Industry Promotion Plan (20170309006YY), Jilin Province Scientific Technology Project of Traditional Chinese Medicine(2019129).