Schizandrin inhibits fibrosis and epithelial-mesenchymal transition in transforming growth factor-β1-stimulated AML12 cells.

Abstract

The transforming growth factor (TGF)-β1 plays a crucial role in the induction of the epithelial-to-mesenchymal transition (EMT) in hepatocytes, which contributes to the pathogenesis of liver fibrosis. The inhibition of the TGF-β1 cascade suppresses EMT and the resultant fibrosis. Schizandrin (Sch) has various therapeutic effects on a range of medical conditions such as anti-asthmatic, anti-cancer, and anti-inflammatory effects. However, the effect of Sch on TGF-β1-stimulated hepatic fibrosis and EMT is still unknown. In the present investigation, we evaluated the anti-fibrotic and anti-EMT properties of Sch and its underlying mechanisms in murine hepatocyte AML12 cells. Overall, we found that Sch inhibited the pro-fibrotic activity of TGF-β1 in AML12 cells; thus, it suppressed the accumulation of ECM proteins. Also, Sch inhibited the EMT as assessed by reduced expression of vimentin and fibronectin, and increased E-cadherin and ZO-1 in TGF-β1 induced AML12 cells. Sch reduced TGF-β1-mediated phosphorylation of Smad2/3 and Smad3/4 DNA binding activity. On the other hand, Sch reduced TGF-β1-induced ERK1/2 and PI3K/Akt phosphorylation in the non-Smad pathway. In conclusion, Sch can antagonize TGF-β1-mediated fibrosis and EMT in AML12 cells. Sch may possess potential as an anti-fibrotic molecule in the treatment of liver fibrosis.

• Authors: Ji-hyun Park, Jaewoo Yoon
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 25 Issue 2 Pg. 276-84 (Apr 2015) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 25701504 (Publication Type: Journal Article)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Cyclooctanes
• Lignans
• Polycyclic Compounds
• RNA, Small Interfering
• Smad2 Protein
• Smad2 protein, mouse
• Smad3 Protein
• Smad3 protein, mouse
• Smad4 Protein
• Smad4 protein, mouse
• Transforming Growth Factor beta1
• Phosphatidylinositol 3-Kinases
• Mitogen-Activated Protein Kinases
• schizandrin

Topics

• Animals
• Cell Line
• Cyclooctanes (pharmacology)
• Epithelial-Mesenchymal Transition (drug effects)
• Fibrosis
• Lignans (pharmacology)
• Liver Diseases
• Mice
• Mitogen-Activated Protein Kinases (antagonists & inhibitors, genetics)
• Phosphatidylinositol 3-Kinases (metabolism)
• Polycyclic Compounds (pharmacology)
• RNA, Small Interfering (genetics)
• Smad2 Protein (metabolism)
• Smad3 Protein (metabolism)
• Smad4 Protein (metabolism)
• Transforming Growth Factor beta1 (metabolism)