Smad6 suppresses the growth and self-renewal of hepatic progenitor cells.

Ding ZY, Liang HF, Jin GN, Chen WX, Wang W, Datta PK, Zhang MZ, Zhang B, Chen XP
J Cell Physiol. 2014 229 (5): 651-60

PMID: 24446200 · DOI:10.1002/jcp.24488

Activation of hepatic progenitor cells (HPCs) is commonly observed in chronic liver disease and Wnt/β-catenin signaling plays a crucial role in the expansion of HPCs. However, the molecular mechanisms that regulate the activation of Wnt/β-catenin signaling in the liver, especially in HPCs, remain largely elusive. Here, we reported that ectopic expression of Smad6 suppressed the proliferation and self-renewal of WB-F344 cells, a HPC cell line. Mechanistically, we found that Smad6 inhibited Wnt/β-catenin signaling through promoting the interaction of C-terminal binding protein (CtBP) with β-catenin/T-cell factor (TCF) complex to inhibit β-catenin mediated transcriptional activation in WB-F344 cells. We used siRNA targeting β-catenin to demonstrate that Wnt/β-catenin signaling was required for the proliferation and self-renewal of HPCs. Taken together, these results suggest that Smad6 is a regulatory molecule which regulates the proliferation, self-renewal and Wnt/β-catenin signaling in HPCs.

© 2013 Wiley Periodicals, Inc.

MeSH Terms (11)

Animals beta Catenin Cell Line Cell Proliferation Gene Expression Regulation Liver Liver Regeneration Rats Smad6 Protein Stem Cells Wnt Signaling Pathway

Connections (2)

This publication is referenced by other Labnodes entities:

Links