Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8304965 | Biochimie | 2015 | 9 Pages |
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.
Keywords
PI3KTGF-β1Type-I collagenERKAP-1ZO-1GeniposideMAPKSp-1transforming growth factorTransforming growth factor β1EMTphosphoinositide-3 kinaseFibrosisSpecificity protein 1Zonula occludens-1Hepatocyteactivator protein 1mitogen-activated protein kinaseextracellular signal-regulated kinaseEpithelial–mesenchymal transition
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Authors
Ji-Hyun Park, Jaewoo Yoon, Ki Yong Lee, Byoungduck Park,