Activin A induces growth arrest through a SMAD- dependent pathway in hepatic progenitor cells.
Activin A induces growth arrest through a SMAD- dependent pathway in hepatic progenitor cells.
复制标题
激活素 A 通过 SMAD 依赖性途径诱导肝祖细胞生长停滞
DOI：
10.1186/1478-811x-12-18
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发表时间：
2014-03-17
期刊：
影响因子：
--
通讯作者：
Chen XP
中科院分区：
文献类型：
--
作者：
Chen L;Zhang W;Liang HF;Zhou QF;Ding ZY;Yang HQ;Liu WB;Wu YH;Man Q;Zhang BX;Chen XP
激活素A是转化生长因子-β超家族的重要成员，具有抑制成熟肝细胞增殖的作用。然而，激活素A对肝祖细胞生长的影响尚未完全了解。为此，我们试图评估激活素A在调节肝祖细胞增殖中的潜在作用。使用2-乙酰氨基芴/部分肝切除术模型，激活素A表达在部分肝切除术后立即降低，然后在术后第9天至第15天增加，这与卵圆细胞增殖的减弱有关。激活素A通过激活SMAD信号通路抑制人卵圆细胞株LE 6的生长，表现为SMAD 2/3磷酸化，Rb磷酸化抑制，cyclinD 1和cyclinE抑制，p21 WAF 1/Cip 1和p15 INK 4 B表达上调。用激活素A拮抗剂卵泡抑素或阻断SMAD信号转导可减弱激活素A的抗增殖作用。相比之下，MAPK通路的抑制并不有助于这种效果。在2-乙酰氨基芴/部分肝切除模型中，通过给予卵泡抑素拮抗激活素A活性增强卵圆细胞增殖。激活素A通过SMAD途径起作用，负调节肝祖细胞的增殖。
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.
影响因子：
4.5
作者：
Park DY;Suh KS
通讯作者：
Suh KS