Smad6 Suppresses the Growth and Self-Renewal of Hepatic Progenitor Cells

• Published in: Journal of cellular physiology Vol. 229; no. 5; pp. 651 - 660
• Main Authors: Ding, Ze-Yang, Liang, Hui-Fang, Jin, Guan-Nan, Chen, Wei-Xun, Wang, Wei, Datta, Pran K., Zhang, Ming-Zhi, Zhang, Bixiang, Chen, Xiao-Ping
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.05.2014; Wiley Subscription Services, Inc
• Subjects: Animals; beta Catenin - genetics; beta Catenin - metabolism; Cell Line; Cell Proliferation; Gene Expression Regulation; Liver - cytology; Liver Regeneration - physiology; Rats; Smad6 Protein - pharmacology; Stem Cells - cytology; Stem Cells - physiology; Wnt Signaling Pathway - physiology
• ISSN: 0021-9541; 1097-4652
• 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. J. Cell. Physiol. 229: 651–660, 2014. © 2013 Wiley Periodicals, Inc.