Elk-3 Contributes to the Progression of Liver Fibrosis by Regulating the Epithelial-Mesenchymal Transition

이천주; 김성민; 허원희; 최정은; 김정희; 홍성우; 이은별; 이준호; 윤성규

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자료유형: 학술저널

저자정보: 이천주 김성민 허원희 최정은 김정희 홍성우 이은별 이준호 윤성규

저널정보: 거트앤리버 발행위원회 Gut and Liver Gut and Liver 제11권 제1호

발행연도: 2017.1

수록면: 102 - 111 (10page)

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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 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.

#Epithelial-mesenchymal transition #Elk-3 #Liver cirrhosis #Early growth response-1 #MAPK pathway

참고문헌 (26)

참고문헌 신청

Ayadi A / 2001 / Net, an Ets ternary complex transcription factor, is expressed in sites of vasculogenesis, angiogenesis, and chondrogenesis during mouse development / Mech

Beaussier M / 2007 / Prominent contribution of portal mesenchymal cells to liver fibrosis in ischemic and obstructive cholestatic injuries / Lab Invest 87 : 292 ~ 303

Braddock M / 2001 / The transcription factor Egr-1: a potential drug in wound healing and tissue repair / Ann Med 33 : 313 ~ 318

Coleman DL / 1992 / Lipopolysaccharide induces Egr-1 mRNA and protein in murine peritoneal macrophages / J Immunol 149 : 3045 ~ 3051

Friedman SL / 1985 / Hepatic lipocytes: the principal collagen-producing cells of normal rat liver / Proc Natl Acad Sci U S A 82 : 8681 ~ 8685

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