Effects of geniposide on hepatocytes undergoing epithelial-mesenchymal transition in hepatic fibrosis by targeting TGFβ/Smad and ERK-MAPK signaling pathways.

Abstract

Liver fibrosis results from increased deposition of type-I collagen within the hepatic extracellular space and constitutes a common cardinal signature in all forms of liver injury, regardless of etiology. Transforming growth factor β1 (TGF-β1) plays a crucial role in the pathogenesis of liver fibrosis. Geniposide is recognized as being useful against hyperlipidemia and fatty liver. However, its cellular mechanism and anti-fibrotic effect in TGF-β1-induced hepatocytes have not been explored. In the present study, we investigated its anti-epithelial-mesenchymal transition (EMT) mechanism by examining the effect of geniposide on TGF-β1-induced hepatocytes. The effect of geniposide on TGF-β1-induced AML12 cells was assessed using Western blotting, quantitative real-time PCR, immunofluorescence staining and DNA binding activity. We found that geniposide significantly inhibited TGF-β1-induced mRNA and protein expression of type-I collagen. Cells treated concurrently with TGF-β1 and geniposide retained high levels of localized E-cadherin expression with no increase in vimentin. Treatment with geniposide almost completely blocked the phosphorylation of Smad2/3, extracellular signal-regulated kinase (ERK) and Akt in AML12 cells. Taken together, these results suggest that geniposide may suppress TGF-β1-induced EMT in hepatic fibrosis by inhibiting the TGFβ/Smad and ERK-mitogen-activated protein kinase (MAPK) signaling pathways. Our results may help researchers better understand the pathogenesis of liver fibrosis so they can develop novel therapeutic strategies for treatment of liver diseases.

• Authors: Ji-Hyun Park, Jaewoo Yoon, Ki Yong Lee, Byoungduck Park
• Journal: Biochimie (Biochimie) Vol. 113 Pg. 26-34 (Jun 2015) ISSN: 1638-6183 [Electronic] France
• PMID: 25818617 (Publication Type: Journal Article, Retracted Publication)
• Copyright: Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Chemical References

• Iridoids
• Smad2 Protein
• Smad2 protein, mouse
• Smad3 Protein
• Smad3 protein, mouse
• Tgfb1 protein, mouse
• Transforming Growth Factor beta1
• geniposide
• Extracellular Signal-Regulated MAP Kinases

Topics

• Animals
• Cell Line
• Epithelial-Mesenchymal Transition (drug effects)
• Extracellular Signal-Regulated MAP Kinases (genetics, metabolism)
• Hepatocytes (metabolism, pathology)
• Iridoids (pharmacology)
• Liver Cirrhosis (drug therapy, genetics, metabolism, pathology)
• MAP Kinase Signaling System (drug effects, genetics)
• Mice
• Smad2 Protein (genetics, metabolism)
• Smad3 Protein (genetics, metabolism)
• Transforming Growth Factor beta1 (genetics, metabolism)