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- Title
Elk-3 Contributes to the Progression of Liver Fibrosis by Regulating the Epithelial-Mesenchymal Transition.
- Authors
Tian Zhu Li; Sung Min Kim; Wonhee Hur; Jung Eun Choi; Jung-Hee Kim; Sung Woo Hong; Eun Byul Lee; Joon Ho Lee; Seung Kew Yoon
- 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 an in 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.
- Subjects
HEPATIC fibrosis; SOMATIC embryogenesis; TRANSFORMING growth factors-beta; GENE silencing; CIRRHOSIS of the liver; DNA-protein interactions; SMALL interfering RNA; PROGNOSIS; THERAPEUTICS; IMMUNOLOGY
- Publication
Gut & Liver, 2017, Vol 11, Issue 1, p102
- ISSN
1976-2283
- Publication type
Article
- DOI
10.5009/gnl15566