Activin A-Smad Signaling Mediates Connective Tissue Growth Factor Synthesis in Liver Progenitor Cells

被引:17
|
作者
Ding, Ze-Yang [1 ]
Jin, Guan-Nan [1 ,2 ]
Wang, Wei [1 ]
Sun, Yi-Min [1 ]
Chen, Wei-Xun [1 ]
Chen, Lin [1 ]
Liang, Hui-Fang [1 ]
Datta, Pran K. [3 ]
Zhang, Ming-Zhi [4 ]
Zhang, Bixiang [1 ]
Chen, Xiao-Ping [1 ]
机构
[1] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Hepat Surg Ctr, Wuhan 430030, Peoples R China
[2] Huazhong Univ Sci & Technol, Union Hosp, Dept Nephrol, Tongji Med Coll, Wuhan 430030, Peoples R China
[3] Univ Alabama Birmingham, Div Hematol & Oncol, Dept Med, Birmingham, AL 35294 USA
[4] Vanderbilt Univ, Dept Med, Div Nephrol & Hypertens, 221 Kirkland Hall, Nashville, TN 37235 USA
来源
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2016年 / 17卷 / 03期
关键词
Activin A; liver fibrosis; connective tissue growth factor; oval cell; Smad proteins; HEPATIC STELLATE CELLS; FACTOR CTGF/CCN2 EXPRESSION; FACTOR-BETA; HEPATOCELLULAR-CARCINOMA; OVAL CELL; STEM/PROGENITOR CELLS; TGF-BETA; MATURE HEPATOCYTES; DUCTULAR REACTIONS; RAT-LIVER;
D O I
10.3390/ijms17030408
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页数:16
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