PMID- 27011166
OWN - NLM
STAT- MEDLINE
DCOM- 20161213
LR  - 20191023
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 17
IP  - 3
DP  - 2016 Mar 22
TI  - Activin A-Smad Signaling Mediates Connective Tissue Growth Factor Synthesis in 
      Liver Progenitor Cells.
PG  - 408
LID - 10.3390/ijms17030408 [doi]
LID - 408
AB  - Liver progenitor cells (LPCs) are activated in chronic liver damage and may 
      contribute to liver fibrosis. Our previous investigation reported that LPCs 
      produced connective tissue growth factor (CTGF/CCN2), an inducer of liver 
      fibrosis, yet the regulatory mechanism of the production of CTGF/CCN2 in LPCs 
      remains elusive. In this study, we report that Activin A is an inducer of 
      CTGF/CCN2 in LPCs. Here we show that expression of both Activin A and CTGF/CCN2 
      were upregulated in the cirrhotic liver, and the expression of Activin A 
      positively correlates with that of CTGF/CCN2 in liver tissues. We go on to show 
      that Activin A induced de novo synthesis of CTGF/CCN2 in LPC cell lines LE/6 and 
      WB-F344. Furthermore, Activin A contributed to autonomous production of CTGF/CCN2 
      in liver progenitor cells (LPCs) via activation of the Smad signaling pathway. 
      Smad2, 3 and 4 were all required for this induction. Collectively, these results 
      provide evidence for the fibrotic role of LPCs in the liver and suggest that the 
      Activin A-Smad-CTGF/CCN2 signaling in LPCs may be a therapeutic target of liver 
      fibrosis.
FAU - Ding, Ze-Yang
AU  - Ding ZY
AD  - Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan 430030, China. 
      dingzeyang@hust.edu.cn.
FAU - Jin, Guan-Nan
AU  - Jin GN
AD  - Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan 430030, China. jgnlh@163.com.
AD  - Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan 430030, China. jgnlh@163.com.
FAU - Wang, Wei
AU  - Wang W
AD  - Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan 430030, China. freeskywang@163.com.
FAU - Sun, Yi-Min
AU  - Sun YM
AD  - Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan 430030, China. sunyimin224@163.com.
FAU - Chen, Wei-Xun
AU  - Chen WX
AD  - Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan 430030, China. 
      chenweixunclark@163.com.
FAU - Chen, Lin
AU  - Chen L
AD  - Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan 430030, China. chenlin_tj@126.com.
FAU - Liang, Hui-Fang
AU  - Liang HF
AD  - Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan 430030, China. 
      lianghuifang1997@126.com.
FAU - Datta, Pran K
AU  - Datta PK
AD  - Division of Hematology and Oncology, Department of Medicine, University of 
      Alabama at Birmingham, Birmingham, AL 35294, USA. dattapk@uab.edu.
FAU - Zhang, Ming-Zhi
AU  - Zhang MZ
AD  - Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt 
      University, Nashville, TN 37235, USA. ming-zhi.zhang@vanderbilt.edu.
FAU - Zhang, Bixiang
AU  - Zhang B
AD  - Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan 430030, China. 
      bixiangzhang@tjh.tjmu.edu.cn.
FAU - Chen, Xiao-Ping
AU  - Chen XP
AD  - Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan 430030, China. 
      xpchen@tjh.tjmu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160322
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (CCN2 protein, human)
RN  - 0 (Smad Proteins)
RN  - 0 (activin A)
RN  - 104625-48-1 (Activins)
RN  - 139568-91-5 (Connective Tissue Growth Factor)
SB  - IM
MH  - Activins/genetics/*metabolism
MH  - Adult Stem Cells/*metabolism
MH  - Animals
MH  - Case-Control Studies
MH  - Connective Tissue Growth Factor/genetics/*metabolism
MH  - HEK293 Cells
MH  - Humans
MH  - Liver Cirrhosis/*metabolism/pathology
MH  - Rats
MH  - Signal Transduction
MH  - Smad Proteins/*metabolism
MH  - Up-Regulation
PMC - PMC4813263
OTO - NOTNLM
OT  - Activin A
OT  - Smad proteins
OT  - connective tissue growth factor
OT  - liver fibrosis
OT  - oval cell
EDAT- 2016/03/25 06:00
MHDA- 2016/12/15 06:00
PMCR- 2016/03/01
CRDT- 2016/03/25 06:00
PHST- 2015/12/10 00:00 [received]
PHST- 2016/03/02 00:00 [revised]
PHST- 2016/03/02 00:00 [accepted]
PHST- 2016/03/25 06:00 [entrez]
PHST- 2016/03/25 06:00 [pubmed]
PHST- 2016/12/15 06:00 [medline]
PHST- 2016/03/01 00:00 [pmc-release]
AID - ijms17030408 [pii]
AID - ijms-17-00408 [pii]
AID - 10.3390/ijms17030408 [doi]
PST - epublish
SO  - Int J Mol Sci. 2016 Mar 22;17(3):408. doi: 10.3390/ijms17030408.