Activin A induces growth arrest through a SMAD- dependent pathway in hepatic progenitor cells

• Published in: Cell communication and signaling 2014-03, Vol.12 (1), p.18-18
• Main Authors: Chen, Lin, Zhang, Wei, Liang, Hui-fang, Zhou, Qiao-fan, Ding, Ze-yang, Yang, Hong-qiang, Liu, Wei-bo, Wu, Yan-hui, Man, Quan, Zhang, Bi-xiang, Chen, Xiao-ping
• Format: Article
• Language: English
• Subjects: Activins - antagonists & inhibitors; Activins - genetics; Activins - metabolism; Animals; Bone morphogenetic proteins; Cell Line; Cell Proliferation; Colleges & universities; Cyclin D1 - metabolism; Cyclin E - metabolism; Cyclin-Dependent Kinase Inhibitor p15 - genetics; Cyclin-Dependent Kinase Inhibitor p15 - metabolism; Cyclin-Dependent Kinase Inhibitor p21 - genetics; Cyclin-Dependent Kinase Inhibitor p21 - metabolism; Follistatin - pharmacology; Genetic aspects; Growth; Hepatocytes - metabolism; Hepatocytes - physiology; Kinases; Medical research; Physiological aspects; Rats; Rodents; Scientific equipment and supplies industry; Signal Transduction; Smad Proteins - metabolism; Stem Cells - metabolism; Stem Cells - physiology
• ISSN: 1478-811X; 1478-811X
• DOI: 10.1186/1478-811x-12-18

Activin A, an important member of transforming growth factor-β superfamily, is reported to inhibit proliferation of mature hepatocyte. However, the effect of activin A on growth of hepatic progenitor cells is not fully understood. To that end, we attempted to evaluate the potential role of activin A in the regulation of hepatic progenitor cell proliferation. Using the 2-acetaminofluorene/partial hepatectomy model, activin A expression decreased immediately after partial hepatectomy and then increased from the 9th to 15th day post surgery, which is associated with the attenuation of oval cell proliferation. Activin A inhibited oval cell line LE6 growth via activating the SMAD signaling pathway, which manifested as the phosphorylation of SMAD2/3, the inhibition of Rb phosphorylation, the suppression of cyclinD1 and cyclinE, and the promotion of p21WAF1/Cip1 and p15INK4B expression. Treatment with activin A antagonist follistatin or blocking SMAD signaling could diminish the anti-proliferative effect of activin A. By contrast, inhibition of the MAPK pathway did not contribute to this effect. Antagonizing activin A activity by follistatin administration enhanced oval cell proliferation in the 2-acetylaminofluorene/partial hepatectomy model. Activin A, acting through the SMAD pathway, negatively regulates the proliferation of hepatic progenitor cells.