Elk-3 Contributes to the Progression of Liver Fibrosis by Regulating the Epithelial-Mesenchymal Transition
Gut and Liver
;
: 102-111, 2017.
Article
Dans Anglais
| WPRIM
| ID: wpr-85470
ABSTRACT
BACKGROUND/AIMS:
The role of Elk-3 in the epithelial-mesenchymal transition (EMT) during liver fibrogenesis remains unclear. Here, we determined the expression of Elk-3 in in vitro and in vivo models and in human liver fibrotic tissues. We also investigated the molecular relationships among Elk-3, early growth response-1 (Egr-1), and the mitogen activated protein kinases (MAPK) pathway during EMT in hepatocytes.METHODS:
We established anin vitro EMT model in which normal mouse hepatocyte cell lines were treated with transforming growth factor (TGF)-β1 and a CCl4-induced liver fibrosis model. Characteristics of EMT were determined by evaluating the expression levels of related markers. The expression of Elk-3 and its target Egr-1 were analyzed using Western blotting. Gene silencing of Elk-3 was performed using an siRNA knockdown system.RESULTS:
The expression levels of mesenchymal markers were increased during TGF-β1-induced EMT of hepatocytes. The expression levels of Elk-3 and Egr-1 were significantly (p<0.05) increased during the EMT of hepatocytes, in CCl₄-induced mouse liver fibrotic tissues, and in human liver cirrhotic tissues. Silencing of Elk-3 and inhibition of the Ras-Elk-3 pathway with an inhibitor suppressed the expression of EMT-related markers. Moreover, Elk-3 expression was regulated by p38 MAPK phosphorylation during EMT.CONCLUSIONS:
Elk-3 contributes to the progression of liver fibrosis by modulating the EMT via the regulation of Egr-1 under MAPK signaling.
Texte intégral:
Disponible
Indice:
WPRIM (Pacifique occidental)
Sujet Principal:
Phosphorylation
/
Techniques in vitro
/
Facteurs de croissance transformants
/
Lignée cellulaire
/
Technique de Western
/
Mitogen-Activated Protein Kinases
/
Extinction de l'expression des gènes
/
Hépatocytes
/
Petit ARN interférent
/
P38 Mitogen-Activated Protein Kinases
Type d'étude:
Étude pronostique
Limites du sujet:
Animaux
/
Humains
langue:
Anglais
Texte intégral:
Gut and Liver
Année:
2017
Type:
Article
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