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

被引:22
作者
Ding, Ze-Yang [1 ]
Liang, Hui-Fang [1 ]
Jin, Guan-Nan [1 ,2 ]
Chen, Wei-Xun [1 ]
Wang, Wei [1 ]
Datta, Pran K. [3 ]
Zhang, Ming-Zhi [4 ,5 ]
Zhang, Bixiang [1 ]
Chen, Xiao-Ping [1 ]
机构
[1] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Hepat Surg Ctr, Wuhan 430030, Peoples R China
[2] Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Dept Nephrol, Wuhan 430030, Peoples R China
[3] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA
[4] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA
[5] Vanderbilt Univ, Sch Med, Dept Canc Biol, Nashville, TN 37212 USA
基金
中国国家自然科学基金;
关键词
TUMOR-INITIATING CELLS; OVAL CELL; FACTOR-BETA; HEPATOCELLULAR-CARCINOMA; TRANSCRIPTIONAL ACTIVITY; LIVER-REGENERATION; STEM-CELLS; ACTIVATION; INHIBITION; DIFFERENTIATION;
D O I
10.1002/jcp.24488
中图分类号
Q2 [细胞生物学];
学科分类号
071013 [干细胞生物学];
摘要
Activation of hepatic progenitor cells (HPCs) is commonly observed in chronic liver disease and Wnt/-catenin signaling plays a crucial role in the expansion of HPCs. However, the molecular mechanisms that regulate the activation of Wnt/-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/-catenin signaling through promoting the interaction of C-terminal binding protein (CtBP) with -catenin/T-cell factor (TCF) complex to inhibit -catenin mediated transcriptional activation in WB-F344 cells. We used siRNA targeting -catenin to demonstrate that Wnt/-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/-catenin signaling in HPCs. J. Cell. Physiol. 229: 651-660, 2014. (c) 2013 Wiley Periodicals, Inc.
引用
收藏
页码:651 / 660
页数:10
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