Smad6 suppresses the growth and self-renewal of hepatic progenitor cells.
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.
Hepatic Surgery Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Ze-Yang
ZY
Ding
Hui-Fang
HF
Liang
Guan-Nan
GN
Jin
Wei-Xun
WX
Chen
Wei
W
Wang
Pran K
PK
Datta
Ming-Zhi
MZ
Zhang
Bixiang
B
Zhang
Xiao-Ping
XP
Chen
D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D008099:Liver / Q000166:cytology*; D008115:Liver Regeneration / Q000502:physiology; D051381:Rats; D051905:Smad6 Protein / Q000494:pharmacology*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D060449:Wnt Signaling Pathway / Q000502:physiology; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
D051905:Smad6 Protein; D051176:beta Catenin