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Updated: Apr 8, 2026

Induction and Analysis of Epithelial to Mesenchymal Transition
Published on: August 27, 2013
Dual roles of MAPK-mediated C/EBPβ phosphorylation in promoting maturation and suppressing EMT during hepatocyte
Shoupei Liu1,2,3, Xiangting Cao1,2, Haibin Wu1,2,3
1Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510006, China.
Abstract:
Human embryonic stem cell (hESC)-derived hepatocytes (hEHs) display functional deficits, particularly impaired albumin secretion and ammonia metabolism, compared to primary human hepatocytes (PHHs). Here, we investigated the regulatory role of CCAAT/enhancer-binding protein beta (C/EBPβ) in hepatocyte maturation. Forced C/EBPβ expression enhanced hepatocyte functionality and upregulated hepatocyte-specific genes, while suppressing epithelial-mesenchymal transition (EMT) via downregulating canonical EMT markers. Mechanistically, CUT&Tag and luciferase reporter assays confirmed C/EBPβ directly bound to the promoter regions of CDH1 (E-cadherin) and CPS1 (carbamoyl phosphate synthetase 1). Co-immunoprecipitation identified an interaction between C/EBPβ and the MAPK pathway. RNA interference combined with Western blot analysis revealed that MAPK1-mediated phosphorylation of C/EBPβ at Thr-235 augmented its transactivation activity, accelerating hepatocyte maturation. Our findings establish C/EBPβ as a master regulator that coordinates transcriptional networks and post-translational modifications during hEHs maturation, providing novel insights for generating mature hepatocytes for disease modeling and regenerative medicine applications.
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