Antagonistic Roles Of TGF-β/Smad And EGFR/AKT Signaling In Epithelial-mesenchymal Transition Program In Hepatic Progenitor Cells

Objectives: To investigate the roles of roles of TGF-β/Smad and EGFR/AKT signaling in epithelial-mesenchymal transition program in hepatic progenitor cells.Methods: We used TGF-β1 to treat hepatic progenitor cells(HPCs)for three days.We imaged the morphology of HPCs by fluorescent light and detected the markers of epithelial and mesenchymal by western blotting to validate whether TGF-β1 induce EMT in hepatic progenitor cells.We used western blotting to detect the phosphorylation state of Smads under TGF-β1 treatment.We investigated the phosphorylation state of Smad3,which has bidirectional roles by different phosphorylation sites.We queried how TGF-β1 phosphorylated the linker sites of Smad3.We detected the phosphorylation status of EGFR under TGF-β1 treatment.We tested whether EGFR phosphorylated AKT by using the specific prohibitor of EGFR.Then,we tested whether EGFR/AKT signaling played a role in the phosphorylation of Samd3 in LINKER sites by using the specific prohibitor of PI3 K.We validated whether TGF-β1 induced EMT when EGFR/AKT signaling was blocked.Conclusion: TGF-β1 couldn’t induce EMT in hepatic progenitor cells apparently.In hepatic progenitor cells,TGF-β/EGFR/AKT signaling antagonized TGF-β/Smad signaling.The canonical TGF-β/Smad signaling phosphorylated the C-terminal of Smad3 to induce EMT.In hepatic progenitor cells,TGF-β/EGFR/AKT signaling phosphorylated LINKER sites to antagonize the role of phosphorylation in C terminal in Smad3,making the TGF-βinduced EMT blocked in hepatic progenitor cells.This finding contributes to a further understanding of mechanism of liver fibrosis and liver carcinoma development and provides a promising cure for targeted therapy.