Conflicts of interest: nothing to declare.
Original Research Article
Smad6 Suppresses the Growth and Self-Renewal of Hepatic Progenitor Cells
Version of Record online: 21 JAN 2014
© 2013 Wiley Periodicals, Inc.
Journal of Cellular Physiology
Volume 229, Issue 5, pages 651–660, May 2014
How to Cite
Ding, Z.-Y., Liang, H.-F., Jin, G.-N., Chen, W.-X., Wang, W., Datta, P. K., Zhang, M.-Z., Zhang, B. and Chen, X.-P. (2014), Smad6 Suppresses the Growth and Self-Renewal of Hepatic Progenitor Cells. J. Cell. Physiol., 229: 651–660. doi: 10.1002/jcp.24488
Ze-Yang Ding, Hui-Fang Liang, and Guan-Nan Jin contributed equally to this work.
- Issue online: 21 JAN 2014
- Version of Record online: 21 JAN 2014
- Accepted manuscript online: 8 OCT 2013 03:22AM EST
- Manuscript Accepted: 2 OCT 2013
- Manuscript Received: 23 JAN 2013
- National Natural Science Foundation of China. Grant Numbers: 30973498, 81072001
- State Key Project on Infection Disease of China. Grant Numbers: 2012ZX10002016-004, 2012ZX10002010-001-004
- Chinese Ministry of Public Health for Key Clinical Project. Grant Number:  493–51
- Graduate Practice Base of Innovation and Enterprise, Huazhong University of Science and Technology. Grant Numbers: HF-09-34-2011-540, 2011JC065
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. J. Cell. Physiol. 229: 651–660, 2014. © 2013 Wiley Periodicals, Inc.