KMID : 1188320170110010102
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Gut and Liver 2017 Volume.11 No. 1 p.102 ~ p.111
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Elk-3 Contributes to the Progression of Liver Fibrosis by Regulating the Epithelial-Mesenchymal Transition
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Li Tian Zhu
Kim Sung-Min Hur Won-Hee Choi Jung-Eun Kim Jung-Hee Hong Sung-Woo Lee Eun-Byul Lee Joon-Ho Yoon Seung-Kew
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Abstract
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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)-¥â1 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-¥â1-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.
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KEYWORD
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Epithelial-mesenchymal transition, Elk-3, Liver cirrhosis, Early growth response-1, MAPK pathway
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