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

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.

journal_name

J Cell Physiol

authors

Ding ZY,Liang HF,Jin GN,Chen WX,Wang W,Datta PK,Zhang MZ,Zhang B,Chen XP

doi

10.1002/jcp.24488

subject

Has Abstract

pub_date

2014-05-01 00:00:00

pages

651-60

issue

5

eissn

0021-9541

issn

1097-4652

journal_volume

229

pub_type

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