期刊
CELL COMMUNICATION AND SIGNALING
卷 12, 期 -, 页码 -出版社
BIOMED CENTRAL LTD
DOI: 10.1186/1478-811X-12-18
关键词
Hepatic progenitor cell; Activin A; follistatin; Proliferation; Smads protein
类别
资金
- National Natural Science Foundation of China [30872499, 81300575, 81372495, 81372327, 81202300]
- state key project on inflectional disease of China [2008ZX1002-25, 2012ZX10002016-004, 2012ZX10002010-001-004]
Background: Activin A, an important member of transforming growth factor-beta 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. Results: 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 p21(WAF1/Cip1) and p15(INK4B) 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. Conclusion: Activin A, acting through the SMAD pathway, negatively regulates the proliferation of hepatic progenitor cells.
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