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

Academic Article

Abstract

  • 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.
  • Keywords

  • Activin A, Smad proteins, connective tissue growth factor, liver fibrosis, oval cell, Activins, Adult Stem Cells, Animals, Case-Control Studies, Connective Tissue Growth Factor, HEK293 Cells, Humans, Liver Cirrhosis, Rats, Signal Transduction, Smad Proteins, Up-Regulation
  • Digital Object Identifier (doi)

    Author List

  • Ding Z-Y; Jin G-N; Wang W; Sun Y-M; Chen W-X; Chen L; Liang H-F; Datta PK; Zhang M-Z; Zhang B
  • Start Page

  • 408
  • Volume

  • 17
  • Issue

  • 3