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

• Published in: International journal of molecular sciences 2016-03, Vol.17 (3), p.408-408
• Main Authors: Ding, Ze-Yang, Jin, Guan-Nan, Wang, Wei, Sun, Yi-Min, Chen, Wei-Xun, Chen, Lin, Liang, Hui-Fang, Datta, Pran K, Zhang, Ming-Zhi, Zhang, Bixiang, Chen, Xiao-Ping
• Format: Article
• Language: English
• Subjects: Activin A; Activins - genetics; Activins - metabolism; Adult Stem Cells - metabolism; Animals; Case-Control Studies; connective tissue growth factor; Connective Tissue Growth Factor - genetics; Connective Tissue Growth Factor - metabolism; HEK293 Cells; Humans; Liver Cirrhosis - metabolism; Liver Cirrhosis - pathology; liver fibrosis; oval cell; Rats; Signal Transduction; Smad proteins; Smad Proteins - metabolism; Up-Regulation
• ISSN: 1422-0067; 1422-0067
• DOI: 10.3390/ijms17030408

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.