Activin A induces growth arrest through a SMAD- dependent pathway in hepatic progenitor cells.
Cell Commun Signal
; 12: 18, 2014 Mar 17.
Article
em En
| MEDLINE
| ID: mdl-24628936
ABSTRACT
BACKGROUND:
Activin A, an important member of transforming growth factor-ß 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 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.CONCLUSION:
Activin A, acting through the SMAD pathway, negatively regulates the proliferation of hepatic progenitor cells.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco
/
Hepatócitos
/
Ativinas
/
Proliferação de Células
/
Proteínas Smad
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article