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

Academic Article

Abstract

  • 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.
  • Published In

    Keywords

  • Animals, Cell Line, Cell Proliferation, Gene Expression Regulation, Liver, Liver Regeneration, Rats, Smad6 Protein, Stem Cells, Wnt Signaling Pathway, beta Catenin
  • Digital Object Identifier (doi)

    Author List

  • Ding Z-Y; Liang H-F; Jin G-N; Chen W-X; Wang W; Datta PK; Zhang M-Z; Zhang B; Chen X-P
  • Start Page

  • 651
  • End Page

  • 660
  • Volume

  • 229
  • Issue

  • 5